Colorado Center for Drug Discovery (C2D2)
Organization: Colorado State University Res Foundation
C2D2 is part of a State of Colorado-sponsored initiative to generate economic development based on bioscience research (HB-08-1001) that is creating a unique academic drug discovery model which will be available to researchers within Colorado. Utilizing the scientific expertise and resources which exist at Colorado research institutions, C2D2 fosters multi-disciplinary and inter-institutional drug discovery collaborations. Through the combination of collaborations, providing drug discovery expertise, and establishing key elements of drug ...
Organization: Yet2.Com Inc
Organization: Yet2.Com Inc
Colorado Center for Drug Discovery (C2D2)
Organization: CSU Ventures Inc
C2D2 is part of a State of Colorado-sponsored initiative to generate economic
development based on bioscience research (HB-08-1001) that is creating a unique academic drug discovery model which will be available to researchers within Colorado. Utilizing the scientific expertise and resources which exist at Colorado research institutions, C2D2 fosters multi-disciplinary and inter-institutional drug discovery collaborations. Through the combination of collaborations, providing drug discovery expertise, and establishing key elements of drug ...
Organization: Auburn University
Organization: University of Missouri St Louis
The Medicinal Chemistry Group at UMSL, which is staffed by chemists with extensive pharmaceutical industry experience, collaborates with and conducts fee-for-service work for industry and academic researchers providing chemistry services. The MCG possesses a full complement of synthesis, purification and analytical tools to ensure high quality results.
>Synthesis of compounds
>Strategy, design, synthesis of new molecules
>Targeted library design and synthesis
>Process development, route optimization
>Custom synthesis
>Lead ...
Biology, Medicine and Pharmaceutical
Organization: NDSU Research Foundation
Although NDSU does not have a medical school, it has advanced capabilities in the areas of biology, medicine, and pharmaceutical sciences.
The NDSU Biological Sciences Department is dedicated to the process of scientific discovery through original research. Our research, both basic and applied, contributes to state, national, and international issues. Financial and related resource support for research is sought from private and public sources. Results of research activities are made available through publication in refereed journals, ...
Coatings & Polymeric Materials
Organization: NDSU Research Foundation
The Coatings and Polymeric Materials department is seated in the College of Science and Mathematics at North Dakota State University. The department provides the only academic research focused on polymer organic coatings in North America, and is one of only very few such departments in the world. The focus on polymer coatings at NDSU goes back to 1905, when many paints were based on vegetable oils and lead pigments.
Our Research Specialties include:
• Polymer, organic chemistry, responsive/structured polymers, nanomaterial ...
Mizzou Advantage - One Health/One Medicine
Organization: University of Missouri Columbia
Mizzou is one of only five universities in the nation with law, medicine, veterinary medicine and a nuclear research reactor on one campus. In conjunction with world-class research centers for swine and small rodent genetics, these resources create an ideal environment for translational medicine.
Researchers at MU’s Comparative Orthopaedic Laboratory performed the first surgeries to regenerate damaged tissue in dog knees. The procedure is now ready for human clinical trials.
MU is one of 20 members in the National Cancer Institute’s ...
Organization: University of Mississippi
http://www.research.olemiss.edu/sites/default/files/Antinfectives.pdf
Introduction
The Research Institute of Pharmaceutical Sciences (RIPS), within the School of Pharmacy, was established in 1964 to discover and disseminate knowledge of natural drug products, develop and commercialize new products, improve public health and stimulate the economy. The major research component of RIPS is the National Center for Natural Products Research (NCNPR). The NCNPR is the nation's only university-affiliated research center devoted to discovering, ...
Organization: University of Mississippi
http://www.research.olemiss.edu/sites/default/files/Botanicals.pdf
Introduction
The Research Institute of Pharmaceutical Sciences (RIPS), within the School of Pharmacy, was established in 1964 to discover and disseminate knowledge of natural drug products, develop and commercialize new products, improve public health and stimulate the economy. The major research component of RIPS is the National Center for Natural Products Research (NCNPR). The NCNPR is located in the Thad Cochran Research Center and is the nation's only ...
Organization: University of Mississippi
Introduction
The Research Institute of Pharmaceutical Sciences (RIPS), within the School of Pharmacy, was established in 1964 to discover and disseminate knowledge of natural drug products, develop and commercialize new products, improve public health and stimulate the economy. With the establishment of the Center of Research Excellence in Natural Products Neuroscience (CORE-NPN), investigators at the University of Mississippi are able to synergize with the resources provided through the NCNPR to conduct state-of-the-art research aimed at ...
High Throughput Method to Evaluate Enzymes Related to Lipid Production
Organization: University of Alberta
Researchers at the University of Alberta have developed a method to detect and quantify the efficacy of enzymes involved in TAG synthesis. Because the method is done in situ, it uses minimal materials and processing steps. The technology is amenable to high-throughput screening of enzymes, fatty acid substrates, and modulators of TAG production, all without the use of hazardous materials.
Method for Modulating Microbial Quorum Sensing
Organization: Wisconsin Alumni Research Foundation (WARF)
Bacteria that use quorum sensing are thought to be involved in two thirds of human bacterial infections. These bacteria produce acyl-homoserine lactones (AHL), which they use to gauge population density. When the population reaches a sufficient density, virulence genes are induced and certain pathogens produce protective biofilms. Therefore, quorum sensing controls genes that are essential to inducing infections caused by diverse bacteria. UW-Madison researchers have developed methods and compounds that reduce virulence by stimulating or ...
Novel Candidates for an Improved Tuberculosis Vaccine
Organization: Wisconsin Alumni Research Foundation (WARF)
Approximately one-third of the world’s population is infected with the bacterium Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Five to 10 percent of non-immunocompromised individuals infected with M. tuberculosis will develop active TB during their lifetimes. TB ultimately causes 1.7 million deaths every year and is a leading cause of death of individuals infected with the human immunodeficiency virus (HIV). A vaccine for tuberculosis has been developed and is used routinely worldwide. ...
Improved Production of Influenza Virus, Including H1N1, for Vaccine Manufacture
Organization: Wisconsin Alumni Research Foundation (WARF)
The H1N1 influenza virus, known as the “swine flu,” has been declared a pandemic. While this virus is less virulent than many circulating strains of flu virus, it has become the subject of significant public health efforts, including international stockpiling of vaccine. However, this virus is less amenable to high titer production than many of the more common influenza viruses, making vaccine manufacture challenging. UW-Madison researchers have identified a single point mutation in the haemagglutinin (HA) gene of the ...
An Injectable Nanovehicle for a Cancer Treatment Combination of Paclitaxel, Rapamycin and 17-AAG
Organization: Wisconsin Alumni Research Foundation (WARF)
Two-drug combinations of paclitaxel and rapamycin (an mTOR inhibitor) as well as paclitaxel and 17-AAG (an enhanced version of geldanamycin and Hsp90 inhibitor) have progressed into human clinical trials for cancer therapy. UW-Madison researchers have discovered that paclitaxel, rapamycin and 17-AAG exert synergistic anticancer activity against breast cancer cells. They also have discovered that nontoxic, nanoscale poly(ethylene glycol)-block-poly(lactic acid), or PEG-b-PLA, micelles surprisingly can take up all three cancer drugs, enabling ...
Novel Antibacterial Agents That Modulate Quorum Sensing and Are Effective at Physiological pH
Organization: Wisconsin Alumni Research Foundation (WARF)
Quorum sensing is a process used by some bacteria to coordinate behavior based on local population density. To communicate, bacteria release signaling molecules into the environment. When a certain number of signaling molecules accumulates and the population reaches a sufficient density, the bacteria change their behavior to work together for a common goal. For example, they may adapt to the nutrients that are currently available, defend against other microorganisms or protect themselves from toxic compounds. Agents that interfere with ...
Benzodiazepine Derivatives with Reduced Side Effects for Treatment of Neuropathic Pain
Organization: Wisconsin Alumni Research Foundation (WARF)
Neuropathic pain encompasses a wide range of painful conditions of diverse origins, including diabetic neuropathy, post herpatic neuralgia, post-surgical nerve injuries and many others. Currently there are five approved drugs on the market to treat the diversity of neuropathic pain conditions; however, they are not effective for all patients and may have adverse side effects. Researchers at the University of Wisconsin-Milwaukee have developed new benzodiazepine derivatives useful in the treatment of neuropathic pain with reduced sedative and ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Although it is essential to healthy brain function, the blood-brain barrier (BBB) interferes with drug delivery, preventing more than 98 percent of small molecule pharmaceuticals and nearly 100 percent of protein and gene therapeutics from entering the brain from the bloodstream. This makes the treatment of brain disorders such as stroke, Alzheimer’s disease or brain tumors difficult. Accurately reproducing the blood-brain barrier in an in vitro setting would help identify compounds capable of entering the brain; however, this ...
Vitamin D Analog for Preventing and Treating Renal Disease, Particularly Lupus Nephritis
Organization: Wisconsin Alumni Research Foundation (WARF)
Renal disease is an increasingly important health problem worldwide. The annual cost of kidney disease in the U.S. alone is more than $42 billion. Systemic lupus erythematosus is a multigenic, non-organ-specific autoimmune disorder. Lupus nephritis is the manifestation of lupus in the kidney. Lupus nephritis occurs frequently in individuals with systemic lupus erythematosus and generally progresses to chronic kidney failure in five to 10 years. 1α,25-dihydroxyvitamin D3 has been shown to effectively reduce the ...
Crystallized Vitamin D Compound Known as “20DCM”
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Attenuated Influenza Viruses for Development of Live Influenza Vaccine
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza is a major disease in humans that can be prevented by vaccination. Because new epidemic strains arise every year or two, influenza vaccines must be adapted almost every year. Live attenuated vaccines, which contain pathogens that have been modified so they no longer cause disease, generally induce a more effective immune response than other types of vaccines. A UW-Madison researcher previously developed attenuated influenza virus strains with mutations in the ion channel protein M2 and the surface-exposed membrane channel ...
Vitamin D Analog “N-23” for Cancer Prevention and Treatment
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analog for Cancer Prevention and Treatment
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analog “Me-Cvit” Potentially Useful to Inhibit Hypercalcemia, Treat Cancer
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analogs “DO-REVA” and “DO-REVB” for Cancer Prevention and Treatment
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Small Molecule Therapeutics to Inhibit HPV Infection
Organization: Wisconsin Alumni Research Foundation (WARF)
Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens. These small DNA viruses are associated with almost all cervical cancers and 20 to 30 percent of head and neck cancers. Cervical cancer is the second most common cancer in women worldwide. It is a major cause of morbidity and mortality. Head and neck cancer is the fourth most frequent cancer worldwide and the sixth most common cancer in the U.S. The survival rate is less than 50 percent, and that statistic has not improved in decades. Vaccines against HPV have ...
HIV Vaccine Induces Broad Immunogenic Response, Reduces Viral Load
Organization: Wisconsin Alumni Research Foundation (WARF)
More than 33 million people worldwide currently are infected with the human immunodeficiency virus (HIV), which causes AIDS. Despite more than 20 years of intense research, a broadly effective vaccine against AIDS has not yet been developed. A major obstacle to the development of a vaccine is the variability of HIV. Current vaccine strategies use DNA or recombinant viral vectors to induce immune responses to whole HIV genes or large gene fragments. However, vaccine immunogens based on single strains of HIV are ineffective ...
Slow Release Retinoic Acid Ester Compounds for Treating Skin Disorders
Organization: Wisconsin Alumni Research Foundation (WARF)
Retinoids are natural and synthetic compounds that are structurally related to vitamin A. All-trans retinoic acid (atRA) is the functional form of vitamin A that regulates growth, cellular differentiation and embryonic development. Because atRA is such a potent regulatory molecule, it is formed in limited amounts and is rapidly metabolized. Various forms of atRA and synthetic retinoids have been used to treat skin conditions, including acne, psoriasis and cancer, as well as to reduce skin atrophy caused by corticosteroid ...
Novel Broad-Spectrum Antifungal Therapeutics That Target Histidine Kinases
Organization: Wisconsin Alumni Research Foundation (WARF)
The incidence of invasive fungal infection has increased as the number of immunocompromised patients has increased. Patients at greater risk for severe fungal disease include those undergoing administration of broad-spectrum antibiotics, corticosteroids and cytotoxic agents; intravenous catheters; invasive medical procedures; and infection with the human immunodeficiency virus. Treatments for fungal infection have been developed; however, many currently available antifungal therapies are highly toxic. Additionally, ...
Compound to Treat Staphylococcus aureus Infections Including MRSA Strains
Organization: Wisconsin Alumni Research Foundation (WARF)
Emerging resistance to antibiotics remains a serious threat to human health. The Centers for Disease Control and Prevention (CDC) estimates that each year nearly 2 million people acquire an infection while in a hospital. New antimicrobial agents are urgently needed to combat the rise of resistant forms of infections including methicillin-resistant Staphylococcus aureus (MRSA). Two-thirds of the S. aureus strains isolated from infected people are now MRSA strains and are responsible for nearly 278,000 infections and 19,000 deaths annually, ...
Colloidal Magnetic Nanobioparticles—A New Approach to Treating Disease
Organization: Wisconsin Alumni Research Foundation (WARF)
According to the American Cancer Society, cancer kills more than 500,000 people in the United States each year. Many cancers are treatable; however, traditional therapies are invasive and/or cause adverse side effects. Conventional treatments for other diseases, including pathogen-borne illnesses, also can be unpleasant and are not always successful. Attempts to develop therapeutic techniques that result in fewer side effects have not been entirely successful. Magnetic fluid hyperthermia has been used for years to treat cancer. In this ...
Novel Tautomycetin Analogs Specifically Inhibit SHP-2, May Provide New Cancer Treatment
Organization: Wisconsin Alumni Research Foundation (WARF)
SHP-2 is an oncogene from the protein tyrosine phosphatase (PTP) superfamily. Mutations in SHP-2 can cause multiple forms of leukemia and solid tumors, as well as the autosomal dominant disorders Noonan syndrome and Leopard syndrome, making SHP-2 an attractive drug target. However, it has proven difficult to develop SHP-2 inhibitors with optimal potency and pharmacological properties. Tautomycetin (TTN) may provide a promising lead for the development of new immunosuppressive and anti-tumor agents. TTN is a complex ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Many of the compounds used in drug discovery by pharmaceutical companies are glycosylated, bacterial secondary metabolites. A glycosylated metabolite consists of a central core structure (aglycon) and various sugar (glycosyl) attachments. Because the sugar moieties of many of these metabolites define their biological activities, altering the carbohydrate ligands can lead to valuable new pharmaceuticals. A UW–Madison researcher previously developed a glycorandomization method for rapidly generating a diverse library of novel ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Tautomycetin (TTN) is a complex polyketide natural product produced by Streptomyces griseochromogens. It specifically inhibits the protein phosphatases PP1 and PP2A, which are two of the four major serine/threonine phosphatases that regulate an array of cellular processes. Because many human diseases are characterized by an altered interplay between phosphatases and kinases, compounds that selectively inhibit PP1 and PP2A may be useful in the treatment of diseases like cancer. In contrast to other naturally occurring PP1 and PP2A ...
Inhibitors of Ebola and Other Filoviruses
Organization: Wisconsin Alumni Research Foundation (WARF)
Ebola, a negative strand RNA virus in the family Filoviridae, is among the most lethal human pathogens, causing death in 50 to 90 percent of cases. This virus is highly contagious in aerosol form and is one of the most worrisome potential biological weapons. Because no approved vaccines or antivirals are available for use against Ebola or other filoviruses, biosafety level-4 (BSL-4) containment is mandatory for work with these viruses. This limitation has hindered basic research as well as the development of vaccines and large-scale ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Five million people in the U.S. are chronically infected with Hepatitis C virus (HCV). Infection with this RNA virus is the leading cause of liver failure in the U.S. Approximately 60 percent of HCV patients develop chronic liver disease and many of these individuals need a liver transplant. Unfortunately, the virus survives in other cells and infects the new liver upon transplantation. Immunosuppressive agents are given to transplant recipients to minimize rejection; however, use of immunosuppressants has been linked ...
Using P-Selectin to Monitor Asthma
Organization: Wisconsin Alumni Research Foundation (WARF)
Asthma is a chronic disease that affects more than 20 million Americans. Many tests for diagnosing asthma are available, but few options for monitoring treatment efficacy and disease progression exist. And the limited methods that are available are inconsistent, inaccurate and/or tedious. Because asthma is characterized by eosinophilic inflammation, tests that measure proteins associated with eosinophils may provide a new option for monitoring the disease. The inventors previously discovered that beta1 integrin activation ...
Bisphosphonates Inhibit Aneurysm Formation and Growth
Organization: Wisconsin Alumni Research Foundation (WARF)
Aortic aneurysms are weakened or bulging areas in the aorta, the largest blood vessel in the body. As many as 30,000 deaths may result from ruptured abdominal aortic aneurysms each year, but no drug therapy has been shown to be useful to decrease the growth or rupture rate of such aneurysms. Studies have found that mortality can be reduced for patients with large aneurysms through surgical interventions. Surgical interventions do not improve survival rates for small aneurysms, so such patients are monitored but not ...
Library of Glycosylated Chlorambucil Analogs for Cancer Treatment
Organization: Wisconsin Alumni Research Foundation (WARF)
Many of the compounds used in drug discovery by pharmaceutical companies consist of a central core structure (aglycon) and various sugar (glycosyl) attachments. Because the sugar moieties of many of these compounds define their biological activities, altering the carbohydrate ligands can lead to valuable new pharmaceuticals. A UW–Madison researcher previously developed a glycorandomization method for rapidly generating a diverse library of novel glycosylated compounds for use in drug discovery (see WARF reference number ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Wound healing is a complex and dynamic process of rebuilding skin and tissue. Chronic or impaired wounds result when tissues fail to progress through the necessary stages of healing. This is a significant clinical problem, affecting 5.7 million patients in the United States and costing an estimated $20 billion each year. The choice of treatment and the development of novel therapeutics depend on the underlying biology and co-morbidity. Although current understanding of many cellular and molecular processes has advanced substantially, ...
Detecting and Evaluating Angiotensinogen Receptor-Modulating Compounds Using Placental Cells
Organization: Wisconsin Alumni Research Foundation (WARF)
The renin-angiotensin system (circulating RAS) is an essential enzymatic cascade regulating electrolyte balance, body fluid volume, and blood pressure in humans. The circulating RAS is found throughout the bloodstream and has been the target for several successful pharmaceuticals used to control blood pressure and treat cardiac diseases such as hypertension. These pharmaceuticals include β-blockers, angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors. In recent years, tissue-specific RASs have been ...
Human Cytomegalovirus Glycoprotein O as a New Drug Target and Subunit Vaccine Candidate
Organization: Wisconsin Alumni Research Foundation (WARF)
Human cytomegalovirus (CMV) is a significant human pathogen capable of causing diseases that affect all age groups worldwide. Only one drug is known to be effective against CMV; however, it is quite toxic and many patients show resistance to it. There is no protective vaccine against CMV. UW-Madison researchers have developed a method of designing a new anti-CMV drug. CMV is thought to enter cells through a multi-step process, one step of which involves a glycoprotein complex, gCIII. The researchers discovered a glycoprotein, glycoprotein O ...
Peptide Analogs of the VanS Catalytic Center Inhibit VanR Binding to its Cognate Promoter
Organization: Wisconsin Alumni Research Foundation (WARF)
Resistant strains of bacteria are becoming a serious health problem. One antibiotic of special interest is vancomycin, which is significant as an antibiotic of “last resort.” Emergence of vancomycin resistance in bacteria would be catastrophic. Currently, efforts to inhibit the development of antibiotic resistance in bacteria have shown little success. UW-Madison researchers have identified peptides for inhibiting two-component signal transduction systems, including protein systems believed to be responsible for the development ...
Treatment of Systemic Lupus Erythematosis
Organization: Wisconsin Alumni Research Foundation (WARF)
Systemic Lupus Erythematosis (SLE) is a systemic autoimmune disease with the potential to be directly involved in multiple organ systems. Current treatments are potentially toxic and may be ineffective for some high-risk patients. UW-Madison researchers have developed a method of treating SLE in susceptible individuals by administering vitamin D analogs effective to prevent or diminish SLE symptom development, including lymph node swelling and proteinuria. Studies indicate that SLE patients should be on a normal calcium-containing diet where ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Collagen is the most abundant protein in vertebrates. It serves as the fundamental structural protein for vertebrate tissues and is critically important in wound healing. Several types of collagen have been found in mammals. The most abundant types are I and II. Although types V and XI are less common, studies of the different forms of V and XI procollagen chains have revealed causal links between defects in these chains and genetic diseases like Ehlers–Danlos syndrome and Stickler syndrome. UW–Madison researchers ...
Novel Antimicrobial Compounds That May Inhibit Bacterial Resistance
Organization: Wisconsin Alumni Research Foundation (WARF)
Increasing numbers of pathogenic bacteria are becoming resistant to antibiotics. According to the Food and Drug Administration, approximately 70 percent of bacteria that cause infections in hospitals are resistant to at least one of the drugs commonly used to treat infections. The discovery of new antibacterial compounds is critical to fighting infectious disease. One option may be naturally occurring cationic peptides, such as magainins, which adopt secondary structures with both cationic and lipophilic regions. These ...
Cytotoxic T Lymphocyte Epitopes of the Major Outer Membrane Protein of <i>Chlamydia trachomatis</i>
Organization: Wisconsin Alumni Research Foundation (WARF)
C. trachomatis (Ct) is the causative agent of two major human diseases: trachoma, an infectious blindness affecting the mucosa of the eye, and a sexually transmitted disease. HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein (MOMP) of Ct, are present in the peripheral blood of humans with Ct genital tract infections. UW-Madison researchers previously described six HLA-restricted epitopes of MOMP that are promising candidates for inclusion in anti-Ct vaccines. UW-Madison researchers have now identified two ...
Recombinant, Attenuated Vaccine for <i>Blastomyces Dermatitidis</i> to Prevent Fungal Infection
Organization: Wisconsin Alumni Research Foundation (WARF)
Blastomyces dermatitidis and related fungi are found worldwide and produce progressive pulmonary and disseminated infections in both humans and animals (primarily dogs). Infectious B. dermatitidis converts to pathogenic yeast forms in vivo, which produce influenza or pneumonia, and disseminate, resulting in serious damage to the lungs and other organs and death to untreated individuals. Thus, there is the need for an effective vaccine against B. dermatitidis. UW-Madison researchers have successfully engineered an attenuated, ...
Attenuated Viruses with Mutant Ion Channel Protein
Organization: Wisconsin Alumni Research Foundation (WARF)
Ion channels, which control the transport of ions across cell membranes, are essential for many cellular functions and may play an important role in the life cycle of viruses. For example, the M2 protein from influenza type A virus has ion channel activity. Because this protein does not vary among influenza A strains, it was thought to be essential for virus replication. A UW-Madison researcher has developed—for the first time—a mutant virus that does not contain M2 ion channel activity. The recombinant influenza A virus was ...
Synthetic Peptides with Broad Spectrum Antiviral Activity
Organization: Wisconsin Alumni Research Foundation (WARF)
Viruses such as herpes simplex virus (HSV-1 and HSV-2), human papilloma virus (HPV) and human immunodeficiency virus (HIV) cause a variety of diseases. Several peptides that inhibit viruses have been developed in recent years; however, many of these known antiviral peptides are extremely hydrophobic, are only effective against a limited number of viruses, do not prevent initial viral infection and do not function topically. Broad spectrum antivirals that could be applied topically and incorporated into products such as condom lubricants could ...
Method of Targeting Pharmaceuticals to Motor Neurons
Organization: Wisconsin Alumni Research Foundation (WARF)
Even though therapeutic compounds have been developed for nervous system disorders, these conditions remain difficult to treat, largely because of the difficulties associated with delivering drugs to the nervous system. The therapeutics often are insoluble, have short half lives in the blood stream or have high systemic toxicity. UW-Madison researchers have developed a method for delivering therapeutic drugs to motor neurons. This method could be used to treat botulism, which is caused by botulinum neurotoxin, a potentially serious ...
Receptor For <I>Bacillus anthracis</I> Toxin
Organization: Wisconsin Alumni Research Foundation (WARF)
Infection with Bacillus anthracis, the spore-forming causative agent of anthrax, can result in either a generally benign, self-limiting cutaneous disease or a more serious and often fatal systemic disease. The serious, systemic form of anthrax results from the inhalation of spores and is caused by anthrax toxin. Because B. anthracis spores can be inexpensively prepared and delivered as an aerosol to cause the deadly inhalation form of infection, B. anthracis spores have become one of the most dreaded agents of biowarfare and ...
Inhibition of Lipoprotein Secretion
Organization: Wisconsin Alumni Research Foundation (WARF)
Elevated levels of low-density lipoproteins (LDLs) are strongly correlated with severe forms of hypercholesterolemia. Because patients vary in responsiveness to “statins” – drugs that inhibit the activity of a particular enzyme in cholesterol biosynthesis – new treatments for high cholesterol are needed. UW-Madison researchers have developed a novel means to reduce LDL levels in the bloodstream. Described is a gene construct composed of a promoter expressing a fusion protein. The fusion protein contains a truncated ...
Acyclic Isoprenoid Ether Derivatives as Chemotherapeutics
Organization: Wisconsin Alumni Research Foundation (WARF)
Farnesol, an acyclic isoprenoid alcohol naturally found in foods, has shown some ability to suppress tumor growth; however, its action is short-lived because it is converted to prenyl dioic acids and excreted. Gamma-tocotrienol, a farnesol mimetic, suppresses tumor growth much more effectively than farnesol. Although gamma-tocotrienol is not converted to prenyl acids and is therefore not excreted, alpha-tocopherol in the diet markedly diminishes gamma-tocotrienol’s tumor-suppressive action. UW-Madison researchers have developed a ...
Novel Vitamin D Analog Increases Bone Strength and Density
Organization: Wisconsin Alumni Research Foundation (WARF)
Vitamin D (1,25-dihydroxyvitamin D3) is a highly potent regulator of calcium homeostasis and plays an established role in cellular differentiation. A recently discovered class of vitamin D analogs, the 19-nor-vitamin D compounds, shows a selective activity profile with high potency in inducing cellular differentiation, making these analogs potentially useful for treating a number of disorders. UW-Madison researchers have developed a new 19-nor vitamin D compound, 2alpha-methyl-19-nor-20(S)-1alpha,25-dihydroxyvitamin D3 (2AMD). It is ...
A Protein That Binds <i>E. coli</i> 0157:H7 C1 Esterase Inhibitor
Organization: Wisconsin Alumni Research Foundation (WARF)
The most devastating manifestation of cystic fibrosis (CF) is the thickening of the mucus layer in the lungs. This highly viscous mucus, a result of mutations in the CF transmembrane conductance regulator (CFTR) gene, leads to increased incidence of respiratory infection. Frequent infections lead, in turn, to a cycle of inflammation and obstruction of normal lung function. Despite decades of study and a detailed understanding of the molecular basis of the disease, state-of-the-art treatment for CF remains limited. ...
Cytoskeletal-Active Agents for Glaucoma Therapy
Organization: Wisconsin Alumni Research Foundation (WARF)
Glaucoma is the second leading cause of visual impairment and the fourth leading cause of blindness in the United States. Although several therapies for glaucoma currently exist, these can be inconvenient (e.g., need to be applied several times daily), uncomfortable for patients to use and have unwanted systemic effects. UW-Madison researchers have developed an ophthalmic preparation of a non-corneotoxic macrolide, such as latrunculin-A, latrunculin-B, swinholide-A and/or jasplakinolide. These macrolides cause transient, drug-induced ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Collagen, the most abundant protein in vertebrates, serves as the fundamental structural protein for vertebrate tissues. Collagen is a fibrous protein consisting of three polypeptide chains that fold into a triple helix. Many diseases including arthritis, atherosclerosis, rheumatism, osteoporosis and osteogenesis imperfecta are linked to collagen abnormalities. UW-Madison researchers have developed a novel, hyperstable collagen mimic. This new collagen mimic consists of a tripeptide unit with the formula (flpYaaGly)n, where flp is ...
Method for Preventing Superoxide Damage to Cells and Oxygen-Labile Proteins
Organization: Wisconsin Alumni Research Foundation (WARF)
Oxygen ions and radicals generated during aerobic growth result in damage to DNA and ultimately, in aging. Several systems exist to reduce the potential for damage by superoxide radicals, by either preventing the damage or repairing it. UW-Madison researchers have developed a method of protecting cells and oxygen-labile enzymes from oxidative damage. YggX is a protein identified from Salmonella enterica serovar Typhimurium. Elevated levels of the YggX protein increase the resistance of Salmonella enterica to superoxide stress and reduce ...
Methods for Engineering Influenza Viruses to Carry Defined Mutations
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza vaccines are prepared from attenuated, live virus or from killed virus. The immunity resulting from live virus vaccines is generally more durable, effective, and cross-reactive than that from killed virus vaccines; however, the mutations in attenuated, live viruses are often ill defined. A UW-Madison reseasrcher has developed a method of preparing viruses with defined mutations. The method uses a reverse genetics system created by Dr. Kawaoka (see WARF reference number P03252US), which consists of plasmids containing the promoter ...
Recombinant Influenza Vectors with a Pol II Promoter and Ribozymes for Vaccines and Gene Therapy
Organization: Wisconsin Alumni Research Foundation (WARF)
Recombinant, infectious influenza viruses can be used as vaccine and gene therapy vectors; however, producing influenza virus particles is difficult because the influenza genome consists of negative-sense RNA molecules that cannot directly serve as templates in protein synthesis. Virus production normally requires a helper virus that provides needed structural proteins and polymerases. UW-Madison resarchers have developed an improved reverse genetics system for producing influenza virus in vertebrate cells in the absence of helper virus. ...
<i>E. coli</i> O157:H7 Binding Protein to C1 Esterase Inhibitor and Methods of Use
Organization: Wisconsin Alumni Research Foundation (WARF)
Enterohemorrhagic Escherichia coli (EHEC) strains are responsible for an estimated 20,000 cases of diarrheal disease in the United States each year. Hemolytic uremic syndrome (HUS), a severe renal disease, occurs in approximately six percent of individuals infected with EHEC. UW-Madison researchers have developed a pO157:H7 plasmid-specified protein found in E. coli EDL933 and other enterohemorrhagic E. coli, which binds to and cleaves C1-esterase inhibitor. This protein, called StcE, is a metalloprotease associated with aggregation of human ...
Antiviral Peptides and Methods for Inducing Cellular Resistance to Infection
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza virus causes millions of infections each year worldwide and is responsible for up to Human parainfluenza virus (PIV) types 1,2,3 and respiratory syncytial virus (RSV) types A and B are the major viral pathogens responsible for causing severe respiratory tract infections in infants and young children. Approximately 4,000 children less than one year of age die each year in the United States from complications resulting from severe respiratory disease caused by infection with RSV and PIV-3. No currently available product can ...
Monoterpenes and Sesquiterpenes as Chemotherapeutic and Radiation Sensitizers and Immunomodulators
Organization: Wisconsin Alumni Research Foundation (WARF)
Apoptosis (programmed cell death), a major pathway by which tumor cells are destroyed, is mediated either through the action of p53 in cells or by the Fas ligand pathway. In many cancers, disruption of the Fas pathway results in tumor cell resistance to chemotherapeutic agents. Perillyl alcohol (POH), a monocyclic monoterpene found in many fruits and vegetables, induces apoptosis. UW-Madison researchers have developed a method of sensitizing tumor cells to radiation therapy, chemotherapy and immunomodulatory therapy. Tumor cells are first ...
Multiple Vesiculoviral Matrix Proteins That Inhibit Both Nuclear Export and Import
Organization: Wisconsin Alumni Research Foundation (WARF)
The matrix protein (M protein) from vesicular stomatitis virus (VSV) inhibits transport into and out of the nucleus of eukaryotic cells. UW-Madison researchers have identified a fragment of VSV M protein and M proteins from other viral species that can inhibit nucleocytoplasmic transport of RNA, proteins and RNA-protein complexes. A fragment of VSV M protein retains the nucleocytoplasmic transport inhibition activity of full length VSV M protein. M proteins from other vesiculoviruses, such as Chandipura virus (CV) and spring viremia of ...
Method for Delivering Molecules to Intracellular Targets
Organization: Wisconsin Alumni Research Foundation (WARF)
Biological membranes are critical for life because they allow cells to regulate entry of water-soluble molecules from the environment. However, these barriers often inhibit the delivery of pharmacologically active molecules to specific targets within cells. UW-Madison researchers have developed beta-peptides and beta-peptide conjugates that are capable of being transported across the cell membranes of living cells. These beta-peptides contain at least six beta-amino acid residues, preferably beta3-homoarginine residues. When a ...
Analogs of Retinamide and Method of Using the Same to Inhibit Neoplastic Cell Growth
Organization: Wisconsin Alumni Research Foundation (WARF)
Retinoic acid (RA), a metabolite of vitamin A, has shown some ability to prevent cancer; however, it is toxic at therapeutic levels. One analog of RA, N-(4-hydroxyphenyl) retinamide-C-glucuronide (HPRCG), has excellent chemopreventative and chemotherapeutic properties; however, it can be metabolized in vivo to yield RA. UW-Madison researchers have developed compounds that exhibit the anti-tumor activity of HPRCG but cannot be hydrolyzed to yield retinoic acid in vivo. In these analogs, the amide bond of HPRCG is replaced with a methylene ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Glaucoma is the second leading cause of visual impairment and fourth leading cause of blindness in the United States. It is often characterized by increased intraocular pressure in the eye, which damages the optic nerve. In the type of glaucoma most prevalent in the West, increased intraocular pressure results from an obstruction in the normal outflow of the aqueous humor through the eye’s trabecular meshwork. UW-Madison researchers have developed a method for reducing intraocular pressure and increasing outflow facility from the eyes ...
High Titer Recombinant Influenza Viruses for Vaccines and Gene Therapy
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza is a major disease in humans that can be prevented by vaccination. Because new epidemic strains arise every year or two, the conventional influenza vaccine must be adapted almost every year, making efficient vaccine production a major objective of pharmaceutical companies. A UW-Madison researcher has developed an efficient technique and system for producing high titer influenza A virus in vertebrate cells in the absence of helper virus. The technology takes advantage of a reverse genetics system created by Dr. Kawaoka that allows ...
Organization: Wisconsin Alumni Research Foundation (WARF)
The emergence of bacteria that are resistant to common therapeutic agents has resulted in a dire need for new antimicrobial compounds. One potential source of new antimicrobials is amphiphilic peptides, which contain both water-soluble and water-insoluble portions. These peptides act by disrupting bacterial membranes. UW-Madison researchers have developed novel amphiphilic compounds that can be used to treat microbial infections in humans and other animals. They combined a synthetic backbone of poly(styrene), poly(acrylate), ...
Metabolic Engineering of Viomycin Biosynthesis
Organization: Wisconsin Alumni Research Foundation (WARF)
The tuberactinomycin (TUB) family of antibiotics is a promising class of drugs for treating antibiotic-resistant infections, such as those caused by multi-drug-resistant tuberculosis (MDR-TB) as well as for targeting catalytic RNAs to disrupt viral replication. TUBs may also be used to treat vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus infections. TUBs are peptide antibiotics containing non-proteinogenic amino acids and are anticipated to be biosynthesized via a non-ribosomal peptide synthetase ...
Reverse Genetics Approach for Generating Ebola Virus and Other Filoviruses from Cloned DNA
Organization: Wisconsin Alumni Research Foundation (WARF)
Ebola virus, a negative strand RNA virus in the family Filoviridae, is among the most lethal human pathogens. Efforts to develop treatments for Ebola infections have been hampered by a lack of effective ways to experimentally mutate the virus. Kawaoka and his colleagues have now developed a reverse genetics approach for generating Ebola virus entirely from cloned cDNA. They prepared the full Ebola genome through reverse transcription of viral RNA, followed by PCR amplification and cloning of Ebola cDNA. They then successfully produced ...
Macrolide Analogs and Methods for Analyzing Them
Organization: Wisconsin Alumni Research Foundation (WARF)
Actin filaments play a key role in the cellular movement needed for wound healing; in the neutralization of bacteria by neutrophils; and in various pathologies, including tumor metastasis, cystic fibrosis, organ infarction and glaucoma. Because of actin’s integral role in disease and injury, there is a growing interest in developing new actin-targeted therapeutics. A UW-Madison researcher has developed methods of identifying macrolide analogs capable of unregulated inhibition of actin filament dynamics. For the methods, ...
Inhibition of Viral Gene Activities
Organization: Wisconsin Alumni Research Foundation (WARF)
Certain viruses, such as Epstein Barr virus, human papilloma virus and herpes simplex virus, infect cells and establish latent infections that, in turn, cause several human diseases, including the cancers Burkett's lymphoma, Hodgkin's disease and cervical carcinoma. Replication of these viruses requires viral looping/linking (L/L) proteins, which bind to two different viral DNA regions and physically link them by looping out the intervening DNA. UW-Madison researchers have developed a method of reducing viral infections by administrating a ...
Solid Phase Synthesis of Arylretinamides
Organization: Wisconsin Alumni Research Foundation (WARF)
Although retinoic acid and a number of its analogs, including arylretinamides, have shown some ability to prevent and treat cancer, toxicity has been a significant obstacle to the development of these compounds. Researchers have developed a solid phase synthetic method for preparing arylretinamides with reduced toxicity and enhanced anti-cancer activity. The method starts by reacting hexachloroacetone with a solvent-suspended, resin-bound triphenylphosphine to yield a suspension containing an activated chlorinating reagent. Retinoic acid is ...
Fusion Proteins for Targeted Delivery of Chemotherapeutic Agents
Organization: Wisconsin Alumni Research Foundation (WARF)
One of the serious drawbacks to many anticancer agents is that they are not specific to tumor cells. Targeted drug delivery using antibodies is a promising approach; however, the use of monoclonal antibodies (mAbs) is not effective due to the mAbs’s large size and non-specific uptake by the liver and reticuloendothelial system. A UW-Madison researcher has developed fusion proteins that act as targeted drug carriers. The proteins are derived from molecules, such as apoproteins, that possess natural drug-binding capabilities. They ...
Polyene Antibiotics with Reduced Toxicity
Organization: Wisconsin Alumni Research Foundation (WARF)
Both superficial and systemic fungal infections are common in immunocompromised patients, such as HIV-infected individuals, patients receiving anticancer therapeutics or immunosuppressive drugs after organ transplants, and the elderly. Despite its low solubility and toxicity problems, the polyene antibiotic amphotericin B (AmB) remains the top choice for treating fungal infections. UW-Madison researchers have developed a method for reducing the toxicity of amphotericin B while retaining its potent antifungal activity. They encapsulated AmB ...
Stable Cell Lines Expressing hERG1a and 1b
Organization: Wisconsin Alumni Research Foundation (WARF)
Cardiac IKr channels are targets associated with inherited and acquired long QT syndrome (LQTS), a disorder that can lead to ventricular arrhythmias. Previously, IKr channels were thought to be composed solely of subunits encoded by the ‘1a’ transcript of the human ether-a-go-go-related gene, or HERG. Since drugs designed for other therapeutic targets may unintentionally block IKr channel activity and cause acquired LQTS, commercially available systems that stably express HERG1a have been used to screen all drugs in development. ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza A virus possesses two surface spike proteins, hemagglutinin (HA) and neuraminidase (NA). HA binds to sialic acid-containing receptors on host cell surfaces. NA cleaves terminal sialic acid residues from the glycoconjugates of host cells, which is necessary for the efficient release of progeny virions. Thus, the receptor-binding activity of HA and the receptor-destroying activity of NA counterbalance each other to allow efficient replication of influenza virus. Because sialic acid plays a key role in the influenza virus ...
Cytomegalovirus Disintegrin-Like Peptides
Organization: Wisconsin Alumni Research Foundation (WARF)
Although human cytomegalovirus (HCMV) is capable of binding, penetrating, and initiating replication in all vertebrate cell types tested, the precise mechanism this virus uses to enter cells remains unknown. Integrins are cell surface receptors involved in the entry of many viruses into cells; however, HCMV does not contain any classic integrin-binding domains. One of the HCMV glycoproteins, glycoprotein B, plays a crucial role in attachment and fusion with the host cell. UW-Madison researchers have developed methods to inhibit the entry of ...
Charge-Dynamic Polymers for Delivering Anionic Compounds, Such as DNA, into Cells
Organization: Wisconsin Alumni Research Foundation (WARF)
The safe and efficient delivery of DNA into cells is essential for the clinical success of gene therapy. Synthetic polymers are considered long-term alternatives to virus-based gene delivery agents because they exhibit low immunogenicities and can be easily modified. Of particular interest are cationic polymers. These molecules spontaneously self-assemble with anionic DNA to form condensed interpolyelectrolyte complexes (IPECs) that cells can efficiently internalize. However, once inside the cell, conventional cationic polymers cannot ...
Method to Increase Feed Efficiency by Reducing Endotoxin-Induced GI Tract Inflammation
Organization: Wisconsin Alumni Research Foundation (WARF)
Pathogenic bacteria in the gastrointestinal tract can induce inflammatory responses that negatively affect the ability of animals to efficiently digest food and absorb nutrients. Endotoxin, a characteristic outer membrane component of Gram-negative bacteria, likely induces inflammatory responses by binding to cellular receptors in an animal’s gastrointestinal tract and forming a signal transduction complex with the toll-like receptor (TLR4) and CD14. UW-Madison researchers have developed a method for improving feed efficiency in ...
Methods for Identifying Agents that Bind the Flap-Tip Helix of RNA Polymerase
Organization: Wisconsin Alumni Research Foundation (WARF)
The enzyme RNA polymerase is essential to all gene transcription and the survival of the cell. One portion of the RNA polymerase beta subunit, called the flap domain, literally functions as a flap to close over and hold the RNA transcript. The domain at the uppermost tip of this flap is called the flap-tip helix. UW-Madison researchers have developed methods for identifying moieties that specifically bind the flap-tip helix of the beta subunit of RNA polymerase. The methods involve labeling the moieties, contacting them with a flap-tip ...
Preparations and Uses of an Endogenous Aryl Hydrocarbon Receptor
Organization: Wisconsin Alumni Research Foundation (WARF)
The aryl hydrocarbon receptor (AhR) is a ligand-inducible transcription factor that mediates a broad spectrum of biological processes. It is a member of the emerging bHLH/PAS (basic Helix-Loop-Helix/Pas-Arnt-Sim) super family of transcription factors. Many synthetic chemical agents are recognized ligands for AhR, but endogenous AhR ligands have not yet been identified. UW-Madison researchers have identified a novel endogenous AhR ligand, 2-(1`H-indole-3`-carbonyl)-thiazole-4-carboxylic acid methyl ester. This AhR ligand likely regulates cell ...
Treatment of Inflammatory Bowel Disease with 2-methylene-19-nor Vitamin D Compounds
Organization: Wisconsin Alumni Research Foundation (WARF)
Inflammatory bowel diseases (IBD) are characterized by chronic intestinal inflammation of obscure origin and refer to two distinct disorders: Crohn’s disease and ulcerative colitis (UC). Current methods of treating IBD, which has no known cure, have many adverse side effects. UW-Madison researchers have developed a method of preventing or treating inflammatory bowel diseases with vitamin D compounds. The compounds used to relieve IBD symptoms belong to a class of vitamin D analogs known as the 2-methylene-19-nor-vitamin D compounds. ...
Multi-Functional Matrix to Promote Wound Healing and for Other Biomedical Applications
Organization: Wisconsin Alumni Research Foundation (WARF)
Wound healing is a complex and dynamic process of rebuilding skin and tissue. Chronic or impaired wounds result when tissues fail to progress through the necessary stages of healing. This is a significant clinical problem, affecting 5.7 million patients in the United States and costing an estimated $20 billion each year. According to the CDC, the cost of trauma-related deaths in U.S. is 2.4 times higher than cancer and cardiovascular diseases combined. By 2020, trauma will equal or surpass communicable diseases as the number one cause of ...
Method of Correcting HERG Channel Dysfunction
Organization: Wisconsin Alumni Research Foundation (WARF)
The human eag-related gene (HERG) encodes a potassium channel that is expressed in the heart. Mutations in the HERG channel are a common cause of long QT syndrome (LQTS), a disorder associated with delayed cardiac repolarization, prolonged electrocardiographic QT intervals and the development of ventricular arrhythmias and sudden death. Defective protein trafficking of mutant HERG channels is a common cause of one form of LQTS. A UW-Madison researcher has developed a method of shortening prolonged QT intervals in a patient with abnormal ...
Yeast Genes That Affect Viral Replication
Organization: Wisconsin Alumni Research Foundation (WARF)
Positive-strand RNA viruses cause several major diseases of animals, plants and humans and show promise as vectors for gene therapy. Many steps in the replication of these viruses depend on specific host factors. UW-Madison researchers have used their knowledge of essential host genes to offer a promising new way to prevent the replication of positive strand RNA viruses. Through the development of a system in which brome mosaic virus (BMV) is able to replicate in yeast (Saccharomyces cerevisiae), they have discovered that mutations in four ...
Method for Inducing Opioid Analgesia and Anesthesia Without Respiratory Suppression
Organization: Wisconsin Alumni Research Foundation (WARF)
Opioid analgesics, which are among the most widely used and effective pain medications, often result in life-threatening respiratory depression when used to treat elderly patients or those suffering from cardiovascular, renal or chronic pulmonary diseases. A UW-Madison researcher has developed a method for reducing or eliminating respiratory depression resulting from use of opioids, without affecting their analgesic or anesthetic effects. The method involves combining an opiate or opioid analgesic or anesthetic with a D1-dopamine ...
Method for Increasing Insulin Sensitivity and Treating and Preventing Type 2 Diabetes
Organization: Wisconsin Alumni Research Foundation (WARF)
Over 90 percent of patients with diabetes have type 2 diabetes. Patients with type 2 diabetes produce insulin but lose the ability to respond to insulin signaling. UW-Madison researchers have developed a method of increasing insulin sensitivity by reducing stearoyl-CoA desaturase-1 (SCD1) activity in diabetes patients. Reducing the amount of SCD1 protein, inhibiting SCD1 enzymatic activity or both can increase insulin sensitivity, providing a way to prevent or treat type 2 diabetes. The researchers found that mice with little or no SCD ...
Use of Glycorandomization to Produce Novel Glycosylated Products for Drug Discovery
Organization: Wisconsin Alumni Research Foundation (WARF)
Many of the compounds used in drug discovery by pharmaceutical companies are glycosylated, bacterial secondary metabolites. A glycosylated metabolite consists of a central core structure (aglycon) and various sugar (glycosyl) attachments. Because the sugar moieties of many of these metabolites define their biological activities, altering the carbohydrate ligands can lead to valuable new pharmaceuticals; however, current methods of generating novel glycosylated metabolites for testing as drug candidates have severe ...
Methods for Synthesizing Natural and “Unnatural” UDP- and TDP-Nucleotides
Organization: Wisconsin Alumni Research Foundation (WARF)
Many current therapeutic drugs originated as glycosylated bacterial secondary metabolites that consist of a central core structure (aglycon) and various sugar (glycosyl) attachments. Nucleotidylyltransferases activate sugar phosphates as nucleotide diphosphosugar (NDP-sugar) donors during metabolite biosynthesis. Because the sugar moieties define the biological activities of many of these metabolites, altering these carbohydrate ligands can produce valuable new pharmaceuticals. However, there is a lack of efficient methods to synthetically ...
Triaryl Cation Antibiotic from Environmental DNA
Organization: Wisconsin Alumni Research Foundation (WARF)
Cultured microorganisms produce an extraordinary array of structurally diverse and useful organic compounds. However, cultured microbes represent only a small fraction of the microbial diversity present in any natural environment. To access the genes and gene products of uncultured microorganisms, large amounts of microbial DNA can be isolated directly from soil (environmental DNA) without culturing the microbes. UW-Madison researchers have developed triaryl cationic compounds obtained from uncultured soil microorganisms, which exhibit ...
Use of Neuropeptides for Ligament Healing
Organization: Wisconsin Alumni Research Foundation (WARF)
Ligament healing is a complex problem that is influenced by inflammatory cell responses, extracellular matrix remodeling and chemical mediators. Healing potential varies widely among ligaments, with the anterior cruciate ligament (ACL) having very little healing potential. And even with ligaments that heal well, alterations in the ligament persist for years. UW-Madison researchers have developed a method of using neuropeptides to shorten the healing period and increase the strength of ligaments damaged by traumatic injury, disease or disuse. ...
Vitamin D Analog for the Treatment of Cancer, Psoriasis and Osteoporosis
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Receptor Antagonists for the Treatment of Asthma
Organization: Wisconsin Alumni Research Foundation (WARF)
Asthma is a major medical problem world-wide, particularly in well-developed countries. The incidence and severity of asthma are increasing – approximately six percent of the population of the United States now has asthma. Experiments have shown that administration of vitamin D makes some asthma symptoms worse, suggesting that vitamin D inhibitors may be useful in the treatment of asthma; however, no true in vivo antagonist of vitamin D is currently known. UW-Madison researchers have identified several antagonists of the vitamin D ...
Method for Identifying Inhibitors of Epstein-Barr Viral Protein EBNA-1
Organization: Wisconsin Alumni Research Foundation (WARF)
Epstein-Barr virus (EBV) is associated with a number of cancers. The only viral protein expressed in all EBV-associated diseases is EBV nuclear antigen-1 (EBNA-1), a site-specific DNA binding protein. UW-Madison researchers have developed a method of assaying potential inhibitors of EBNA-1. The method is based on their finding that inhibition of EBNA-1 induces apoptosis in cells infected with EBV, whether the cells are benign or tumor cells. First, an EBV-positive cell line and an EBV-negative cell line are obtained and exposed to a test ...
Collection of Drosophila Mutants with Neurodegenerative Effects
Organization: Wisconsin Alumni Research Foundation (WARF)
Few treatments for neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, have been discovered. In many cases, the molecular basis for neurodegeneration remains unknown. Animal models might be useful for identifying new therapies, but few animal models for these diseases currently are available. Drosophila commonly are used as model organisms. As many as 70 percent of human disease genes have homologues in Drosophila, making these organisms useful for identifying particular ...
Methods for Identifying Neurodegeneration Mutants and Screening Neuroprotective Agents
Organization: Wisconsin Alumni Research Foundation (WARF)
The cellular and molecular mechanisms underlying age-dependent neurodegeneration are poorly understood. Drosophila neurodegeneration mutants would be useful in elucidating these mechanisms; however, a targeted and efficient approach to screening for such mutants is needed. UW-Madison researchers have developed neurodegeneration mutants of Drosophila and a method for obtaining them. The method starts with a collection of temperature-sensitive paralytic or bang-sensitive paralytic mutants, among which are relatively high numbers of ...
Lupeol Anti-Tumor Agent and Its Uses
Organization: Wisconsin Alumni Research Foundation (WARF)
Plants contain thousands of pentacyclic triterpenes, many of which are useful in medicine. Lupeol, the principle constituent triterpene in common fruit plants such as olive, mango, strawberry, and fig, reportedly possesses a wide range of medicinal properties. UW-Madison researchers have developed a method of using Lupeol to prevent, treat or alleviate skin disorders and skin cancers. Lupeol may be administered topically to a patient. Experiments in mice showed that topical application of Lupeol prior to the administration of a drug that ...
Method for Preventing or Treating Cardiac Hypertrophy
Organization: Wisconsin Alumni Research Foundation (WARF)
Cardiac hypertrophy occurs in response to a variety of stimuli that increase stress on the heart, including arterial hypertension, valvular heart disease and familial hypertrophic cardiomyopathy. The condition is characterized by an increase in cardiomyocyte size, enhanced protein synthesis and greater organization of cardiac muscle. Although hypertrophy is an adaptive response that helps sustain cardiac output in the face of stress, prolonged hypertrophy is a significant risk factor for congestive heart failure and subsequent cardiac ...
Method for Treating Glaucoma with C3 Transferase
Organization: Wisconsin Alumni Research Foundation (WARF)
Glaucoma is the second leading cause of visual impairment and fourth leading cause of blindness in the United States. It is often characterized by increased intraocular pressure in the eye, which damages the optic nerve. In the type of glaucoma most prevalent in the West, increased intraocular pressure results from an obstruction in the normal outflow of the aqueous humor through the eye’s trabecular meshwork. UW-Madison researchers have developed a method for reducing intraocular pressure and increasing outflow facility from the eyes ...
Polymer Based Nano-Carriers for the Solubilization and Delivery of Hydrophobic Drugs
Organization: Wisconsin Alumni Research Foundation (WARF)
In addition to being the leading immunosuppressive agent used to reduce the rejection of transplanted organs, Cyclosporine A (CsA) is one of the most effective modulators of drug resistance in cancer treatment. However, acute and chronic toxicities associated with CsA administration have limited its clinical effectiveness in cancer patients. UW-Madison researchers have developed a new, less toxic, formulation of CsA. They encapsulated CsA in poly(ethylene oxide)-b-poly(ε-caprolactone)(PEO-b-PCL) micelles. Micelles are unique among ...
Prostate Cancer Therapeutic Activated under Oxidative Conditions
Organization: Wisconsin Alumni Research Foundation (WARF)
Microorganisms produce a large variety of biologically active secondary metabolites, including polyketides (PK) and non-ribosomal peptides (NRP). Leinamycin (lnm) is a recently identified natural hybrid of PK-NRP that exhibits potent anti-tumor activity in vivo. A UW-Madison researcher has developed a novel analog of lnm, TG-25, for the treatment of prostate cancer. Many cancer drugs, including lnm, fail to effectively treat prostate cancer because prostate cancer cells are under high oxidative stress and the drugs require a reducing ...
Bombesin Peptides for Reducing Impairment of Mucosal Tract Immunity
Organization: Wisconsin Alumni Research Foundation (WARF)
Infections by pathogenic microorganisms frequently cause disease and death in critically ill or injured patients. Among these patients, infections are much more common in those fed intravenously than in those fed through a tube in the stomach or intestine (enteral feeding). Lack of enteral feeding is hypothesized to cause a breakdown of the gastrointestinal barrier and atrophy of gut-associated lymphoid tissue (GALT), allowing molecules and bacteria to enter the body. It also leads to reduced levels of IgA, an important mediator of mucosal ...
Method of Reducing Neural Cell Death
Organization: Wisconsin Alumni Research Foundation (WARF)
Neuronal cell death is a common and irreversible component of many diseases, including neurodegenerative disorders and some ophthalmological disorders, such as glaucoma. UW-Madison researchers have developed a method of reducing neuronal cell death. Neuronal cells are exposed to a boron-protected phenylphosphine, such as bis(3-propionic acid methyl ester)phenylphosphine borane complex or (3-propionic acid methyl ester)diphenylphosphine borane complex. These compounds, successfully tested in rats, are highly neuroprotective at nanomolar and ...
Compositions and Methods for Modulating Angiogenesis
Organization: Wisconsin Alumni Research Foundation (WARF)
Angiogenesis, the development of new blood vessels, is an essential physiological process regulated by multiple endogenous factors. Angiogenesis is a critical pathological development in certain disease states, including rheumatoid arthritis, diabetic retinopathy, macular degeneration, atherosclerosis, psoriasis and tumor growth/metastasis. Conversely, inhibition of blood vessel development characterizes other disease states, such as coronary artery disease, peripheral vascular disease and preeclampsia. UW-Madison researchers have developed ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Insulin is secreted from pancreatic beta cells in response to elevated blood concentrations of glucose and other “secretagogues,” such as amino acids, alpha-ketoacids and mitochondrial metabolites. However, sometimes the beta cells do not respond sufficiently to insulin secretagogues, resulting in Type II diabetes. UW-Madison researchers have developed a method to increase glucose-dependent insulin secretion. They discovered that an analog of alpha-ketoglutarate (alphaKG), which can be converted into the insulin secretagogue ...
Improved Reverse Genetics Method to Produce Influenza Virus
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza causes hundreds of thousands of deaths worldwide every year. Two of the genes critical for influenza virus infection are haemagglutinin (HA) and neuraminidase (NA). HA and NA are on the surface of the virus, and are therefore targets for vaccination. Because classical reassortment methods for producing influenza vaccine are time-consuming and cumbersome, the inventors developed a new method that utilizes “reverse genetics” (see WARF reference number P99264US). For vaccine production, eight plasmids containing the HA ...
Cytotoxic Ribonuclease Variants
Organization: Wisconsin Alumni Research Foundation (WARF)
Ribonucleases are enzymes that catalyze the degradation of RNA. Levels of RNase activity are controlled in vivo by a ribonuclease inhibitor (RI), which binds strongly to an RNase to completely inhibit its catalytic activity. An RNase can be made cytotoxic by modifying its amino acid sequence so RI can’t bind to it. UW-Madison researchers have developed new, highly cytotoxic variants of the bovine ribonuclease A (RNase A) superfamily of ribonucleases. They used the Fast Atomic Density Evaluation (FADE) algorithm for molecular ...
Treatment of Diabetes with Synthetic Beta Cells
Organization: Wisconsin Alumni Research Foundation (WARF)
The insulin-producing beta islet cells of the pancreas are destroyed in people with Type I diabetes, requiring such individuals to inject themselves with exogenous insulin. Replacement of beta cells is a promising alternative to insulin injection, although current methods of replacing beta cells are hindered by limited supply or immune system rejection. UW-Madison researchers have developed a genetic construct capable of providing glucose-regulated expression of insulin when delivered into a suitable host cell, such as a hepatocyte. The ...
Neoglycorandomization and Digitoxin Analogs
Organization: Wisconsin Alumni Research Foundation (WARF)
Many of the compounds used in drug discovery by pharmaceutical companies are glycosylated bacterial secondary metabolites. A glycosylated metabolite consists of a central core structure (aglycon) and various sugar (glycosyl) attachments. Because the sugar moieties of many of these metabolites define their biological activities, altering the carbohydrate ligands through processes such as glycorandomization (see WARF reference number P04020US) can lead to valuable new pharmaceuticals. UW-Madison researchers have now developed a different ...
Common Variants of the Sodium Channel Alpha Subunits
Organization: Wisconsin Alumni Research Foundation (WARF)
The SCN5A gene encodes a human cardiac sodium (Na+) channel alpha subunit that carries the inward Na+ current in the heart. Three distinct polymorphic SCN5A clones, hH1, hH1a and hH1b, have been isolated from human cardiac cDNA libraries. UW-Madison researchers have identified four groups of SCN5A variants that represent the most common SCN5A variants in humans. The researchers found that none of the three previously known SCN5A clones represented a common sequence for SCN5A. The new SCN5A variants, on the other hand, have been observed ...
Compositions and Methods for Treating Neuroendocrine Tumors
Organization: Wisconsin Alumni Research Foundation (WARF)
Neuroendocrine tumors frequently metastasize to the liver. Most patients with hepatic metastases are not candidates for surgery, but there are no other curative treatments and the five-year survival rate is only 30 percent. UW-Madison researchers have developed a method of treating neuroendocrine tumors by inhibiting glycogen synthase kinase 3 (GSK3). GSK3 regulates cell processes including metabolism, cell fate determination, proliferation and survival. When administered to neuroendocrine cancer cells, Li+ and other GSK3 inhibitors ...
Blockade of Pin1 Prevents Cytokine Production by Activated Immune Cells
Organization: Wisconsin Alumni Research Foundation (WARF)
In most individuals, eosinophils have a three-to-four day half-life, but eosinophils isolated from the lungs of asthmatics do not die. Because eosinophils release vasoactive materials and cytokines, which can lead to scarring of lung tissues, reducing their levels may ameliorate asthma symptoms. UW-Madison researchers have developed a method of treating asthma and other immunological disorders associated with eosinophils by administering a Pin1 inhibitor. Pin1 is an enzyme that regulates the cell cycle by targeting certain proteins. ...
Engineering of Ribonuclease Zymogens
Organization: Wisconsin Alumni Research Foundation (WARF)
A zymogen is an inactive enzyme precursor that is converted into an active enzyme by proteolytic activity. UW-Madison researchers have developed a method of engineering an enzyme into a zymogen. They converted the ribonuclease enzyme RNase A into a zymogen by adding a bridge of amino acids that link the amino and carboxyl termini of the enzyme. The bridge contains a protease cleavage site specific to a certain protease. RNase A can be made cytotoxic; thus, this technology suggests how a cytotoxic enzyme, engineered in the form of a zymogen, ...
Modulating Cell Death and Proliferation
Organization: Wisconsin Alumni Research Foundation (WARF)
One approach to treating cancer involves inducing apoptosis (programmed cell death) in tumor cells. Many agents that cause cell death are known, but additional agents are needed to develop more effective cancer therapies. Silent information regulator 2 (Sir2) proteins are highly conserved protein deacetylases that regulate gene silencing, apoptosis, metabolism and aging. Sir2 proteins catalyze a unique protein deacetylation reaction that generates a novel metabolite, O-acetyl-ADP-ribose (OAADPr). The inventors found that OAADPr activates a ...
Method for Controlling the Activity of AMP-Forming Enzymes
Organization: Wisconsin Alumni Research Foundation (WARF)
Many bacteria can use short-chain fatty acid molecules, such as acetate and propionate, for growth. To enter the central metabolic pathways of bacteria, acetate and propionate must first be converted to their respective acyl-coenzyme A forms: acetyl-CoA and propionyl-CoA. In enteric bacteria such as Salmonella enterica and E. coli, this conversion occurs mainly through the action of acetyl-CoA synthetase (Acs) and propionyl-CoA synthetase (PrpE), two members of the family of AMP-forming enzymes (AFEs). UW-Madison researchers have discovered ...
Methods of Forming C-O Bonds by Using a Type II Polyketide Synthase System
Organization: Wisconsin Alumni Research Foundation (WARF)
Polyketides are compounds naturally found in bacteria, fungi and plants that show potential as anti-cancer, antibiotic and immunosuppressant agents. Polyketide synthases (PKSs) are enzymes that synthesize polyketides. These multifunctional enzymes contain different domains, or polypeptides, including ketoacyl synthase (KS), acyl transferase (AT), and acyl carrier proteins (ACP). The polyketide nonactin shows antibiotic activity against Gram-positive bacteria, mycobacteria and fungi. The Type II PKS responsible for biosynthesis of ...
Selective Destruction of Cancer Cells by Mitochondria-Targeting Dyes
Organization: Wisconsin Alumni Research Foundation (WARF)
It has been widely observed that carcinoma membranes exhibit higher electric potentials—more than 60mV—than normal cells. This characteristic means that certain positively charged, or cationic, dye molecules can be driven into diseased tissue and accumulate in cell mitochondria. When exposed to certain wavelengths, the light-activated dyes become toxic to their hosts, triggering cell death or inhibition. Normal cells, able to excrete the dye more efficiently, are largely spared. The uptake and retention of the toxic compounds by cancer ...
Biosynthesis of Enediyne Compounds by Manipulating the C-1027 Gene Pathway
Organization: Wisconsin Alumni Research Foundation (WARF)
A variety of organisms, including Streptomyces carzinostaticus and Streptosporangium pseudovulgare, naturally produce enediyne compounds. These compounds, which possess unusual molecular architectures, significant biological activities and novel modes of action, are of significant interest due to their potential anticancer activities. UW-Madison researchers have now characterized the gene cluster responsible for the biosynthesis of the enediyne C-1027, produced by Streptomyces globisporus. In particular, they have determined the structural ...
A Global Regulator of Secondary Metabolite Biosynthesis in Fungi
Organization: Wisconsin Alumni Research Foundation (WARF)
Secondary metabolites display a broad range of activities, including antibiotic, immunosuppressant, phytotoxic and mycotoxic activities, yet they are formed from a relatively small number of metabolic pathways. UW-Madison researchers have developed a global regulator of secondary metabolism, called LaeA, in fungi. LaeA was identified in the fungus Aspergillus nidulans and subsequently in A. fumigatus. LaeA exerts global control over gene clusters for secondary metabolite biosynthesis, including the penicillin and lovastatin clusters. The ...
Modified Retinoid Compounds with Reduced Toxicity
Organization: Wisconsin Alumni Research Foundation (WARF)
Orally administered retinoic acid isomers are used to treat many disorders; however, they cause serious side effects including weight loss, inanition, eye encrustation, bone loss, mucocutaneous toxicity, hyperlipidemia and teratogenic activity in patients who are pregnant. UW-Madison researchers have developed modified retinoid esters with reduced toxicity. The carboxyl group of a retinoid is esterified with a highly sterically hindered compound, preferably a secondary or tertiary alcohol. The resulting retinoid esters are significantly less ...
TTNPB Analogs Useful for Preventing or Treating Cancer
Organization: Wisconsin Alumni Research Foundation (WARF)
Retinoic acid and a number of its analogs have shown some ability to prevent and treat cancer. One of the most potent is 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl)-1-propenyl]benzoic acid, or TTNPB. However, toxicity has been a significant obstacle to the development of these compounds. UW-Madison researchers have developed less toxic TTNPB analogs for the prevention or treatment of breast cancer. One such analog, 4-HBTTNPB, inhibits the proliferation of tumor cells. Because it binds poorly to the retinoic acid receptor ...
Method of Diminishing the Symptoms of Neurodegenerative Disease
Organization: Wisconsin Alumni Research Foundation (WARF)
Oxidative stress plays a role in the pathology of many neurodegenerative diseases. When a cell experiences an oxidative challenge, the transcription factor Nrf2 activates the antioxidant response element (ARE), which then induces the expression of many genes involved in combating oxidative stress and toxicity. UW-Madison researchers have developed a method of treating neurodegenerative diseases, such as Huntington’s disease, by inducing cellular resistance to oxidative stress. Astrocytes from human brain tissue, or stem cells with the ...
2-Methylene-18,19-Dinor-1Alpha-Hydroxy-Homopregnacalciferol
Organization: Wisconsin Alumni Research Foundation (WARF)
Vitamin D is a highly potent regulator of calcium homeostasis and plays an established role in cellular differentiation. A recently discovered class of vitamin D analogs, the 19-nor-vitamin D compounds, shows a selective activity profile with high potency in inducing cellular differentiation and very low calcium mobilizing activity. These features make the 19-nor compounds potentially useful as therapeutic agents for a number of disorders. UW-Madison researchers have developed a new vitamin D analog, ...
2-Methylene-19-Nor-1Alpha-Hydroxy-17-Ene-Homopregnacalciferol
Organization: Wisconsin Alumni Research Foundation (WARF)
Vitamin D is a highly potent regulator of calcium homeostasis and plays an established role in cellular differentiation. A recently discovered class of vitamin D analogs, the 19-nor-vitamin D compounds, shows a selective activity profile with high potency in inducing cellular differentiation and very low calcium mobilizing activity. These features make the 19-nor compounds potentially useful as therapeutic agents for a number of disorders. UW-Madison researchers have developed a new vitamin D analog, ...
Metalloprotease Activation of Myostatin and Methods of Modulating Myostatin Activity
Organization: Wisconsin Alumni Research Foundation (WARF)
Myostatin, a member of the transforming growth factor-beta (TGF-beta) family, negatively regulates skeletal muscle growth. Myostatin is synthesized as an inactive precursor protein, which is then processed to yield an N-terminal fragment termed the “pro peptide”, and a C-terminal fragment that becomes biologically active myostatin when it forms a disulfide-linked dimer. The pro peptide remains associated with the C-terminal dimer and maintains the dimer in an inactive state. UW-Madison researchers have developed metalloproteases ...
2-Methylene-19,21-Dinor-1Alpha-Hydroxy-Bishomopregnacalciferol
Organization: Wisconsin Alumni Research Foundation (WARF)
Vitamin D is a highly potent regulator of calcium homeostasis and plays an established role in cellular differentiation. A recently discovered class of vitamin D analogs, the 19-nor-vitamin D compounds, shows a selective activity profile with high potency in inducing cellular differentiation and very low calcium mobilizing activity. These features make the 19-nor compounds potentially useful as therapeutic agents for a number of disorders. UW-Madison researchers have developed a new vitamin D analog, ...
Acyltransferases Associated with Type I Polyketide Synthases and Methods of Use
Organization: Wisconsin Alumni Research Foundation (WARF)
Microorganisms produce a large variety of biologically active secondary metabolites, including polyketides (PK) and non-ribosomal peptides (NRP). Genetic manipulation of both PK and NRP biosynthesis has generally been very successful in generating novel products. Leinamycin (Lnm), a recently identified natural hybrid of PK-NRP, exhibits potent in vivo antitumor activity but lacks in vivo stability. UW-Madison researchers have now determined the genetic and biochemical characteristics of the leinamycin biosynthesis gene cluster from ...
Treating Fibrotic Disorders by Inhibiting BMP-1-Like Proteinases
Organization: Wisconsin Alumni Research Foundation (WARF)
The formation of collagen fibrils is essential to the healing of wounds and bone fractures. But excessive formation of collagenous, extracellular matrix (ECM) proteins can cause fibrotic disorders, such as keloids, surgical adhesions or organ-destroying deep-seated fibroses. Bone morphogenetic protein-1 (BMP-1) and BMP-1-like proteinases play a role in creating ECM by cleaving precursor molecules into the mature proteins needed for ECM formation. UW-Madison researchers have devleoped a method of treating fibrotic disorders by inhibiting ...
Use of the T7 Phage Tail Protein Determinant to Target Therapeutics to Hepatocytes <i>In Vivo</i>
Organization: Wisconsin Alumni Research Foundation (WARF)
The T7 bacteriophage is a double-stranded virus that infects E. coli and some strains of Shigella and Pasteurella. UW-Madison researchers have identified a determinant in the T7 phage tail protein that efficiently and specifically targets hepatocytes. Hepatocytes, which are liver cells, perform important roles in metabolism, homeostasis of serum proteins, and the pathogenesis of various metabolic and infectious disorders. Attaching the T7 determinant described in this invention to a therapeutic compound will allow that compound to be ...
Method of Reducing the Toxicity of Retinoids
Organization: Wisconsin Alumni Research Foundation (WARF)
Orally administered retinoic acid isomers are used to treat many disorders; however, they cause serious side effects including weight loss, inanition, eye encrustation, bone loss, mucocutaneous toxicity, hyperlipidemia and teratogenic activity in pregnant mammals. UW-Madison researchers hav developed a method of reducing the toxicity of retinoids containing a free carboxyl group. The carboxyl group of the retinoid is esterified with a highly sterically hindered compound, preferably a secondary or tertiary alcohol. The resulting retinoid ...
Method for Treating or Preventing Steroid-Induced Glaucoma
Organization: Wisconsin Alumni Research Foundation (WARF)
Glaucoma, the second leading cause of blindness worldwide, is characterized by elevated pressure in the eye, damage to the optic nerve head and progressive loss of vision. Following steroid treatment, 40 percent of patients exhibit increased intraocular pressure, a risk factor for glaucoma. Steroid responses in the eye are associated with changes in the actin cytoskeleton known as cross-linked actin networks (CLANs). The cross-linking and subsequent change in cell shape are likely to reduce the normal outflow of fluid from the trabecular ...
Localized Delivery of Nucleic Acid by Polyelectrolyte Assemblies
Organization: Wisconsin Alumni Research Foundation (WARF)
Thin films and coatings that allow the sustained release of DNA from surfaces play an important role in the development of localized approaches to gene therapy. For example, polymer-coated intravascular stents have been used to localize delivery of DNA to the vascular wall and could lead to innovative gene-based treatments for vascular diseases. However, existing devices are coated with relatively thick films of polymers, which can lead to inflammatory responses in vivo. They also utilize DNA encapsulation methods that provide limited ...
Method for Reducing Intraocular Pressure Using Integrin-Linked Kinase Inhibitor
Organization: Wisconsin Alumni Research Foundation (WARF)
Integrin-linked kinase (ILK) is an intracellular protein that plays an important role in connecting integrins to the actin cytoskeleton. UW-Madison researchers have shown that ILK works with phosphatidylinositol 3-kinase (PI3K) to regulate the organization of the actin cytoskeleton in trabecular meshwork cells in the eye, which control the outflow of fluid from the aqueous humor to modulate intraocular pressure. When fluid cannot flow normally from the aqueous humor, intraocular pressure increases and elevates the risk of developing ...
Micelle Composition with Enhanced Drug Loading Capacity and Stability
Organization: Wisconsin Alumni Research Foundation (WARF)
Many powerful drugs have only limited usefulness because they are relatively insoluble in aqueous solutions. For example, the anti-cancer and immunomodulatory compound rapamycin exhibits impressive activity against many tumor models but is difficult to deliver to tumor sites in vivo because of its low solubility. Current methods of delivering such compounds often involve highly toxic solubilization agents, which limit how much of the active compound can be administered. Polymeric micelles, which circulate in the blood for ...
Methods and Compositions for Treating Prostate Cancer Using DNA Vaccines
Organization: Wisconsin Alumni Research Foundation (WARF)
Prostate cancer is a significant health risk for men over the age of 50 and currently is a pervasive health threat with as many as 200,000 new cases diagnosed each year in the US alone. At present, there is no accepted adjuvant treatment for patients undergoing radical prostatectomy or ablative radiation therapy that has been proven to prevent progression to metastatic disease. UW-Madison researchers have developed a new approach for inducing an immune response to a protein critical in the progression of prostate cancer. Their approach ...
Glutarimide-Containing Polyketide Analogs as Drug Leads for Treating Tumor Metastasis
Organization: Wisconsin Alumni Research Foundation (WARF)
Because cell migration plays a critical role in the development of tumor metastasis, inhibiting the migration of tumor cells may provide a new approach to cancer treatment. Compounds containing glutarimide side chains have been shown to inhibit cell migration and vasculature formation. A UW-Madison researcher has developed a library of glutarimide-containing analogs, along with methods of producing them. The analogs, which represent a variety of structures and encompass a range of biological activities, may be used to develop new anti-cancer ...
Spatial Control of Signal Transduction
Organization: Wisconsin Alumni Research Foundation (WARF)
Development of most tissue types involves a complex interplay of multiple growth factors in well defined locations, leading to controlled differentiation of precursor cells into mature, tissue-specific cell types. Ultimately, control over growth factor activity in a three-dimensional construct could allow the growth of hybrid tissues or organs with multiple cell types from a single stem cell precursor. However, existing approaches to growth factor presentation are not conducive to spatial patterning of growth factor activity or sustained ...
Chroman-Derived Anti-Androgens for Treatment of Androgen-Mediated Disorders
Organization: Wisconsin Alumni Research Foundation (WARF)
Androgens (male sex hormones) contribute significantly to the development of prostate cancer. Current anti-androgen hormonal therapies for prostate cancer cause many unpleasant side effects, including impotence, hot flashes, diarrhea, breast enlargement, loss of libido, nausea and toxic liver effects. They can also stimulate prostate cancers in a subset of patients. These side effects occur, in part, because current anti-androgen compounds can cross the blood brain barrier and affect androgen receptors in the central nervous ...
Reducing Bad Cholesterol with Conjugated Linoleic Acid
Organization: Wisconsin Alumni Research Foundation (WARF)
Apolipoprotein B (apo B) is a protein believed to play a role in maintaining ‘bad’ cholesterol in the bloodstream. This type of cholesterol can contribute to plaque buildup in the arteries, called atherosclerosis, a life threatening disease that can lead to heart attack and stroke. A safe dietary method of reducing the amount of apo B secreted from cells into the bloodstream could help treat millions of sufferers and those at risk. The natural food ingredient conjugated linoleic acid (CLA) is a fatty acid shown to be effective in weight ...
Compounds and Methods for Modulating Communication and Virulence in Quorum Sensing Bacteria
Organization: Wisconsin Alumni Research Foundation (WARF)
Many Gram-negative bacteria use quorum sensing to communicate population density through the use of autoinducer ligands like acyl-homoserine lactone (AHL). When density gets high, the bacteria become a community and create a biofilm, which provides a microenvironment conducive to infection. UW-Madison researchers have developed a library of novel compounds that decrease the virulence of quorum sensing bacteria by blocking AHL binding. These non-native natural or synthetic AHL analogs bind to receptors in the cell membrane. With the receptors ...
Cytotoxic Ribonuclease Variants
Organization: Wisconsin Alumni Research Foundation (WARF)
Ribonucleases are enzymes that catalyze the degradation of RNA. Levels of RNase activity are controlled in vivo by a ribonuclease inhibitor (RI), which binds strongly to an RNase to completely inhibit its catalytic activity. An RNase can be made cytotoxic by modifying its amino acid sequence so RI can’t bind to it. UW-Madison researchers have developed new, highly cytotoxic variants of human ribonuclease (RNase 1). They determined—for the first time—the three dimensional atomic crystal structure of human RI (hRI) bound to ...
Bovine P-Selectin Glycoprotein Ligand 1 (BPSGL-1) and Methods of Using Same
Organization: Wisconsin Alumni Research Foundation (WARF)
Binding between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) plays a key role in some inflammatory responses in humans. Human disorders associated with PSGL-1 binding share comparable pathomorphological features with common disorders in cattle, such as enteritis, mastitis, and Haemophilus somnus infection, suggesting that P-selectin/PSGL-1 may play similar roles in animals and humans. A UW-Madison researcher has identified the DNA and protein sequences of bovine PSGL-1. These sequences, which are similar to human and equine ...
Method for Synthesizing Beta-Polypeptides from Functionalized Beta-Lactam Monomers
Organization: Wisconsin Alumni Research Foundation (WARF)
Oligomers and polymers comprised of beta-amino acids, known as beta-peptides, can adopt stable secondary structures that mimic natural peptides. These non-natural compounds are resistant to enzymatic degradation and often exhibit important biological activity. However, large-scale synthesis of beta-peptides is difficult because standard methods involve step-wise, residue-by-residue synthesis. UW-Madison researchers have developed a robust method for making large quantities of poly-beta-peptides under mild and controllable conditions. The ...
Prostate Cancer and Melanoma Screening
Organization: Wisconsin Alumni Research Foundation (WARF)
Almost 200,000 men in the United States develop prostate cancer each year. More than 60,000 people develop melanoma. Early diagnosis is key to survival because the best treatment and prognosis for these diseases depends on early detection. However, diagnostic procedures, such as biopsies or imaging tests, are often invasive and uncomfortable. UW-Madison researchers have developed a minimally invasive method of screening for prostate cancer or melanoma. They identified a number of antigens to which patients with prostate cancer or melanoma ...
Global Regulator of Morphogenesis and Pathogenicity in Dimorphic Fungi
Organization: Wisconsin Alumni Research Foundation (WARF)
Dimorphic fungi are soil-dwelling microorganisms that are harmless in their usual mold form, but once inhaled by a mammal, transform into virulent yeast and cause life threatening illnesses, such as pneumonia and meningitis. Organisms in this class of fungi include Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides immitis, Paracoccidioides brasiliensis, Sporothrix schenckii and Penicillium marneffei. People with compromised immune systems or who are often in close contact with soil, such as military personnel, farm workers and ...
A New Phosphate Binder for Blocking Phosphate Absorption and Reducing Hyperphosphatemia
Organization: Wisconsin Alumni Research Foundation (WARF)
The kidney filters toxins and excess nutrients from the blood. It also synthesizes the active form of vitamin D3. In patients with chronic kidney disease, levels of active vitamin D3 decline, leading to hypocalcemia. At the same time, nutrients, particularly phosphorous, accumulate in the blood. Hypocalcemia and excess phosphorous stimulate the secretion of parathyroid hormone (PTH). PTH can cause excess bone resorption, leading to a condition known as renal osteodystrophy. To prevent renal osteodystrophy, patients who are undergoing ...
Modulating Notch1 Signaling Pathway for Treating Neuroendocrine Tumors
Organization: Wisconsin Alumni Research Foundation (WARF)
Neuroendocrine tumors, which can arise almost anywhere in the body, frequently metastasize to the liver. They are characterized by an increased release of regulatory hormones, which in turn can lead to debilitating symptoms such as asthma, cardiac disease, dehydration and profuse diarrhea. Chemotherapy has had limited success in patients with these tumors, and the only currently successful treatment is surgical removal. UW-Madison researchers have developed a method of activating the Notch1 signaling pathway to treat neuroendocrine tumors, ...
Blood-Brain Barrier Targeting Antibodies
Organization: Wisconsin Alumni Research Foundation (WARF)
Even though therapeutic compounds have been developed for neurologic disorders, such as Alzheimer’s disease, these conditions remain difficult to treat, largely because of the blood-brain barrier. The blood-brain barrier interferes with drug delivery, allowing only those molecules that are lipophilic and have low molecular weight (less than 500 Da) to enter the brain from the bloodstream. More than 98 percent of small molecule pharmaceuticals and nearly 100 percent of protein and gene therapeutics cannot pass through this barrier. ...
Collection of Genomic Fragments That Affect Quorum Sensing
Organization: Wisconsin Alumni Research Foundation (WARF)
Quorum sensing is a process used by some bacteria to coordinate behavior based on local population density. To communicate, bacteria release signaling molecules into the environment. When a certain number of signaling molecules accumulates and the population reaches a sufficient density, the bacteria change their behavior to work together for a common goal. For example, they may adapt to the nutrients that are currently available, defend against other microorganisms or protect themselves from toxic compounds. Agents that interfere with ...
Assay to Detect Susceptibility to Nitrous Oxide Neurologic Syndrome
Organization: Wisconsin Alumni Research Foundation (WARF)
The enzyme 5,10-methylene tetrahydrofolate reductase (MTHFR) plays a role in the synthesis of methionine, an amino acid that is crucial for the production of neurotransmitters, assembly of the myelin sheath, and the synthesis of DNA in proliferating tissues. UW-Madison researchers discovered a novel mutation in the human MTHFR gene that represents a newly recognized pharmacogenetic syndrome, nitrous oxide neurologic syndrome. In this syndrome, nitrous oxide exposure in a genetically predisposed person results in neurological ...
Plasmids Encoding Avian Influenza Genes
Organization: Wisconsin Alumni Research Foundation (WARF)
Avian influenza causes significant economic losses for poultry producers worldwide and can be transmitted to humans and other mammals. The surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) play a key role in infection with this virus. Of the sixteen different HA antigens (H1-H16) and nine different NA antigens (N1-N9), human disease has been caused by the subtypes H1, H2, H3, H5, H7 and H9, and N1 and N2. A UW-Madison researcher has developed plasmids encoding either the H3 N1 or the H5 N2 genes of avian influenza. These genes ...
Novel Mycobacterium Tuberculosis Protein Complex
Organization: Wisconsin Alumni Research Foundation (WARF)
Integral membrane desaturases, which are enzymes that desaturate fatty acids, impact human health and economics because of their contribution to lipid composition and cellular homeostasis. In mammals, these enzymes are important in the development of obesity, diabetes, hypertension, cardiovascular disease, immune disorders, degenerative neurological diseases and skin diseases, among others. In prokaryotes, such as the pathogen Mycobacterium tuberculosis, desaturases play a key role in cell viability. Because the desaturase DesA3 from M. ...
Improved Micellar Delivery System for Hydrophobic or Fluorophilic Drugs
Organization: Wisconsin Alumni Research Foundation (WARF)
Many drugs that are potentially efficacious for treating diseases such as cancer have limited usefulness because they are relatively insoluble and/or toxic. Polymeric micelles can serve as vehicles for the targeted delivery of such compounds. Micelles are unique among drug carrier systems due to their nanoscopic dimensions, hydrophilic shell and hydrophobic core. Encapsulating drugs in micelles results in better control of drug release, lower systemic toxicity and improved solubility. However, conventional micelles comprising only ...
Protein Inhibitor of Ran Activity
Organization: Wisconsin Alumni Research Foundation (WARF)
Proteins and nucleic acids are actively transported in and out of the nucleus through nuclear pores. A small protein called Ran is the gatekeeper for large, complex pore structures. UW-Madison researchers have identified a specific inhibitor of Ran activity. They discovered that the encephalomyocarditis virus leader protein, a small protein with no measurable enzymatic activity, binds directly and specifically to Ran. Expression of this leader protein in human cells inhibits Ran activity, blocking nuclear export of cellular mRNAs and leading ...
Beta-Peptides with Antifungal Activity
Organization: Wisconsin Alumni Research Foundation (WARF)
Fungal infections, such as infections by the yeast Candida albicans, are a persistent health problem in some patient populations. Topical yeast infections affect the mouth, vagina, skin, stomach and urinary tract, producing unpleasant side effects. Systemic infections are a significant and often life-threatening clinical problem, particularly in patients with an indwelling intravascular catheter or those who are immunosuppressed. Both types of C. albicans infections can be treated with Amphotericin B, an antifungal agent that acts by ...
Improved HIV Vaccine Designed to Induce Broad Immune Response Against Subdominant Antigens
Organization: Wisconsin Alumni Research Foundation (WARF)
More than 33 million people worldwide currently are infected with the human immunodeficiency virus (HIV), which causes AIDS. Despite more than 20 years of intense research, a broadly effective vaccine against AIDS has not yet been developed. A major obstacle to the development of a vaccine is the variability of HIV. Current vaccine strategies use DNA or recombinant viral vectors to induce immune responses to whole HIV genes or large gene fragments. However, vaccine immunogens based on single strains of HIV are ...
Antioxidant Compounds for the Prevention and Treatment of Prostate Cancer
Organization: Wisconsin Alumni Research Foundation (WARF)
Oxidative stress is a major contributor to the occurrence and progression of prostate cancer. Reactive oxygen species, such as hydrogen peroxide and hydroxyl free radicals, are found at elevated levels in prostate cancer cells. N1,N4-bis(buta-1,3-dienyl)butane-1,4-diamine, or MDL, is a specific inhibitor of acetyl polyamine oxidase, which plays a key role in producing these reactive oxygen species. UW-Madison researchers have developed a method of using MDL for prostate cancer prevention and treatment. A therapeutic dose of MDL can be given ...
Vitamin D Compounds for the Treatment of Ocular Hypertension
Organization: Wisconsin Alumni Research Foundation (WARF)
Glaucoma, the second leading cause of blindness, is an eye disease that results in optic nerve damage and loss of vision. Glaucoma usually is associated with elevated intraocular pressure (IOP). In individuals with ocular hypertension (OHT), IOP is elevated without optic nerve damage or visual field loss. Such individuals are at greater risk for developing glaucoma. UW–Madison researchers have developed a method of treating OHT by administering a vitamin D analog. The vitamin D compound can be applied topically ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Accurately reproducing the blood-brain barrier in an in vitro setting has been a longstanding challenge. Current methods require the independent isolation of multiple cell types, and the quality of these preparations varies. UW-Madison researchers have developed a simpler, more reproducible in vitro model of the blood-brain barrier. Most existing models include primary brain microvasculature endothelial cells (BMECs), which form the blood-brain barrier in vivo, and the corresponding primary astrocytes, which affect the barrier. The improved ...
Elastin-Like Biopolymers as Delivery Vehicles for Gene Therapy
Organization: Wisconsin Alumni Research Foundation (WARF)
Intelligent biosynthetic nanobiomaterials (IBNs) represent the next evolutionary advance in macromolecular drug delivery—genetically engineered biopolymers. In contrast to traditional polymer macromolecules or viral carriers used for gene and drug delivery, these biopolymers are non-immunogenic and monodisperse, and offer unparalleled control of structural and biophysical characteristics. Designed using an mRNA template, protein-based IBNs contain a polycationic region, a thermosensitive elastin-like polypeptide (ELP) sequence, ...
Antibacterial Agents Using Small Molecule Macroarrays
Organization: Wisconsin Alumni Research Foundation (WARF)
Staphylococcus aureus is a Gram-positive bacterium responsible for many infectious diseases, including toxic shock syndrome, food poisoning and topical skin infections. Although S. aureus is usually amenable to antibiotic treatment, a highly virulent strain, methicillin resistant S. aureus (MRSA), is a leading cause of hospital-acquired infections in the United States. UW-Madison researchers have developed novel chemical agents that exhibit potent antibacterial activity against MRSA and potentially other Gram-positive bacterial pathogens. To ...
High Titer Recombinant Influenza Viruses for Vaccines
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza is caused by the eight-segmented influenza virus. Vaccines can be used to prevent influenza, but traditional methods for producing influenza vaccine are slow and cumbersome. To generate recombinant influenza vaccines, many researchers use an approach developed by the inventor, utilizing “reverse genetics” (see WARF reference number P99264US). In this method, plasmids containing the eight viral RNA segments, along with additional plasmids encoding proteins necessary for replication and transcription, are transfected ...
Use of Peptides of Syndecan-1 to Inhibit Angiogenesis
Organization: Wisconsin Alumni Research Foundation (WARF)
Syndecans, a highly conserved family of four transmembrane heparan sulfate proteoglycans, bind a variety of extracellular matrix ligands, including fibronectin, laminin and vitronectin. Syndecan-1 serves as an important regulator of αvβ3 and αvβ5 integrins, which in turn, are key regulators of adhesion and signaling in numerous biological processes, including cell migration, metastasis and angiogenesis. UW-Madison researchers have identified a novel peptide from the extracellular domain of syndecan-1 that inhibits ...
Methods for Reducing Body Fat Using Vitamin D Compounds
Organization: Wisconsin Alumni Research Foundation (WARF)
In the United States, more than 60 percent of the population is considered overweight or obese. Current treatments, including pharmacological and/or surgical intervention, diet modification and appetite suppression, are not adequate to prevent this growing epidemic. UW-Madison researchers have developed a method of using a vitamin D analog to treat obesity. When administered to an overweight person or other animal, a 2-alkylidene derivative of vitamin D3 effectively maintains or increases lean body mass while reducing overall body weight and ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Collagen, the most abundant protein in vertebrates, provides structure for tissues and plays a key role in wound healing. In connective tissue, individual collagen molecules are wound together in tight triple helices that are further organized into strong fibrils. The collagen polypeptide chains are composed of approximately 300 repeats of the sequence Xaa-Yaa-Gly, where Xaa is often proline (Pro), Yaa is often hydroxyproline (Hyp) and the third residue is always glycine (Gly). Stereoelectronic effects cause the rings in the Xaa and Yaa ...
Tat-Utrophin as a Protein Therapy for Muscular Dystrophies
Organization: Wisconsin Alumni Research Foundation (WARF)
No effective therapy currently exists for the most common and severe form of muscular dystrophy disease, Duchenne Muscular Dystrophy (DMD). This disease, which is characterized by the weakening of voluntary muscles, is caused by the lack of a functional version of the muscle protein dystrophin. Another muscle protein, utrophin, has a similar sequence and has been used to compensate for the loss of dystrophin in a mouse model. However, up-regulating utrophin or increasing the expression of functional dystrophin in muscle cells is difficult ...
Efficient Method of Producing Glass with Enhanced Stability
Organization: Wisconsin Alumni Research Foundation (WARF)
Many drugs that are potentially efficacious for treating diseases, such as cancer, have limited usefulness because they are relatively insoluble. Preparing these drugs in an amorphous, or “glassy,” form improves their solubility. However, they are less stable in this form than in the more commonly used crystalline form. Coating these compounds with a thin layer of vapor-deposited amorphous material is one option to improve their stability. Amorphous materials, such as glass, combine the disordered structure of a liquid with the ...
Efficient Generation of Influenza Virus with Adenoviral Vectors
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza is responsible for hundreds of thousands of deaths worldwide every year. Vaccines can be used to prevent influenza, but traditional methods for producing influenza vaccine are slow and cumbersome. The inventor previously developed a new method of vaccine production that utilizes “reverse genetics” (see WARF reference number P99264US). In this method, eight plasmids containing haemagglutinin (HA) and neuraminidase (NA) genes from circulating or pathogenic strains and the remaining viral genes from “harmless” ...
Method for Assessing 3-D Crystal Structures from <i>in Situ</i> Digital Images
Organization: Wisconsin Alumni Research Foundation (WARF)
Suspension crystallization processes often result in crystals with a wide range of particle sizes. Accurately controlling the distribution of shapes and sizes is a challenge in the pharmaceutical manufacturing industry. Crystal size and shape affect the physical properties that regulate drug dissolution rate, and maintaining particle size distribution within a desired range increases the efficiency of manufacturing and the quality of the end product. To control the crystallization process, the manufacturing industry has developed ...
Treating Cancer by Inhibiting the Interaction of MAGE Protein with KAP-1
Organization: Wisconsin Alumni Research Foundation (WARF)
Because the MAGE family of proteins are expressed in many tumor cells but rarely found in normal cells, they are good potential targets for cancer treatment. Inhibiting the expression or function of MAGE proteins inhibits tumor cell formation and growth. The inventors discovered that multiple MAGE molecules bind to KAP-1, a molecule that in turn binds MDM2, a protein that suppresses p53, a tumor suppressor protein. They showed that suppressing MAGE proteins leads to increased nuclear expression of p53, which promotes apoptosis of tumor ...
Sulfonylurea Receptor Variants from Mitochondria
Organization: Wisconsin Alumni Research Foundation (WARF)
Sulfonylurea receptors (SURs) are a regulatory subunit of ATP-sensitive potassium channels (KATP), and account for major pharmacological differences between KATP in various tissues. At least two isoforms of SUR exist, and the mRNA from each isoform can be spliced in different ways to result in further variants of SUR. The SUR2 isoform encodes the low-affinity sulfonylurea receptor, which is mainly present in mitochondria-rich cardiac, smooth and skeletal muscles. Although their composition is not well understood, mitochondrial KATP channels ...
Nanoparticles That Target Dendritic Cells
Organization: Wisconsin Alumni Research Foundation (WARF)
Dendritic cells play an important role in the process of initiating immune response. They are present in small quantities in tissues, such as skin and lung, that are in contact with the external environment and serve as “border patrols.” Once activated by an antigen, dendritic cells migrate to the lymph tissues where they interact with T and B cells to initiate immune response. As a result, vaccines that stimulate dendritic cells may enhance immunity. UW-Madison researchers have developed a system for delivering vaccines and ...
Organization: Wisconsin Alumni Research Foundation (WARF)
In bacteria, single-stranded DNA binding proteins (SSBs) form essential intermolecular complexes with other DNA replication, recombination and repair proteins. Many, if not all of these interactions are mediated by a short peptide sequence that is highly conserved among bacterial SSBs, but not found in eukaryotic SSBs. If this SSB interaction sequence is mutated or deleted, bacterial viability is drastically reduced. UW-Madison researchers have developed a method for identifying potential antibiotic compounds that block the association of ...
Improved Delivery of Therapeutic Agents
Organization: Wisconsin Alumni Research Foundation (WARF)
Many drugs that are potentially efficacious for treating diseases such as cancer have limited usefulness because they are relatively toxic. Even approved cancer therapeutics can cause adverse side effects such as hypertension, skin disorders and osteoporosis. Gene Directed Enzyme Prodrug Therapy (GDEPT) is a strategy for minimizing the side effects associated with systemic administration of anticancer drugs. GDEPT works by expressing a gene that encodes a prodrug-activating enzyme in tumor cells. Typically, delivery vectors carrying the ...
Materials and Methods for Screening Agents That May Reduce the Risk of Acquired Long QT Syndrome
Organization: Wisconsin Alumni Research Foundation (WARF)
The human ether-a-go-go related gene (HERG) encodes two subunits, HERG 1a and HERG 1b, which form a potassium channel that is expressed in the heart. HERG 1b has a much shorter amino terminus than HERG 1a, and HERG 1b subunits travel to the cell membrane and form functional channels with very low efficiency. Mutations in the HERG 1a subunit are a common cause of long QT syndrome (LQTS), a disorder associated with delayed cardiac repolarization, prolonged electrocardiographic QT intervals and the development of ventricular arrhythmias ...
Calcitonin and Calcitonin-Like Compounds for Multiple Sclerosis
Organization: Wisconsin Alumni Research Foundation (WARF)
Multiple sclerosis (MS) is a complex and unpredictable disease of the central nervous system. MS is thought to be an autoimmune disease in which the immune system attacks and destroys the myelin that insulates the nerves in the brain and spinal cord. When myelin is damaged, the transmission of messages between the brain, spinal cord and body is slowed or blocked, leading to diminished or lost function. No cure for MS has been developed. Several therapies, including anti-inflammatory steroids, naturally occurring antiviral ...
Improved Phage Display System Enables Screening of Liver-Specific Peptides
Organization: Wisconsin Alumni Research Foundation (WARF)
In vivo phage display is a protein library development and screening tool that has proven to be a powerful means of identifying new peptide ligands for specific targeting of organs by drugs and gene therapy vectors. This display system works by incorporating protein libraries into the genome of a bacteriophage, a virus that only infects bacteria. The proteins are incorporated into the coat protein of the virus. Upon expression of the fusion proteins, the phage displays one member of the protein library on its surface. ...
Screening Assay for Agents that Could Prevent or Treat Alzheimer’s Disease
Organization: Wisconsin Alumni Research Foundation (WARF)
The most common form of dementia is Alzheimer’s disease, a progressive and fatal brain disorder. Currently, an estimated 15 million people worldwide suffer from Alzheimer’s disease, and its prevalence is expected to triple by 2050. There is no cure. Beta-amyloid is a protein fragment suspected of disrupting cell-to-cell communication and damaging cells in patients with Alzheimer’s disease. Beta-amyloid is formed when a molecule called amyloid precursor protein (APP) is sequentially cleaved. The first cut is made by the ...
Model System for Identifying Anti-Cancer Agents That Interfere with Gli2
Organization: Wisconsin Alumni Research Foundation (WARF)
Cancer accounts for nearly one quarter of the deaths in the United States each year. Treatment options include radiation, chemotherapy and surgery, among others. However, these treatments often cause debilitating side effects and are not always efficacious. New ways of treating cancer are needed. The glioma-associated (GLI) proteins may provide a new drug target for cancer treatment. These proteins are a family of transcription factors involved in the activation of the highly conserved Hedgehog (Hh) signaling pathway in mammals. In ...
Screen to Determine Effect of Drugs on PFC-Dependent Cognition for ADHD, PTSD and Other Disorders
Organization: Wisconsin Alumni Research Foundation (WARF)
The prefrontal cortex (PFC), which is the most anterior part of the brain, plays a key role in higher cognitive function. Cognitive processes dependent on the PFC are impaired in several disorders and conditions, including attention deficit hyperactivity disorder (ADHD), sleep deprivation, post-traumatic stress disorder (PTSD) and aging. Limited pharmacological treatments that improve PFC-dependent cognition are available. Psychostimulants, such as methylphenidate (MPH, also known as Ritalin) and amphetamine, are the most ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Heat Shock Protein 90 (Hsp90) plays a key role in regulating proteins involved in tumor cell proliferation. Geldanamycin is a promising anti-cancer drug that inhibits Hsp90, but its clinical development has been hampered by poor solubility and liver toxicity. Alternate methods of delivering this compound to tumor sites are needed. A UW-Madison researcher previously developed elastin-like polymer (ELP) fusion constructs for the targeted delivery of therapeutics (see WARF reference number P06346US). The ELP binds and internalizes the ...
Multilayered Film for Delivering Proteins and Other Small Molecules into Cells
Organization: Wisconsin Alumni Research Foundation (WARF)
The ability to deliver proteins into cells has many therapeutic and research applications. However, peptide drugs and therapeutic proteins are notoriously difficult to administer, in part because of the limited permeability and selectivity of the cell membrane. Polyelectrolyte multilayers (PEMs) have been used to deliver biomolecules into cells. PEMs are essentially thin plastic films with alternating layers of positively and negatively charged polymers. Biomolecules, such as nucleic acids, can be integrated into PEMs, which can be designed ...
Coatings That Inhibit Crystallization of Amorphous Drugs to Improve Stability
Organization: Wisconsin Alumni Research Foundation (WARF)
Many drugs that are potentially efficacious for treating diseases, such as cancer, have limited usefulness because they are relatively insoluble. Preparing these drugs in an amorphous, or “glassy,” form improves their solubility and bioavailability. However, they are less stable in this form. Most amorphous drugs crystallize over time, negating their advantages. Typically, amorphous drugs begin crystallizing on the surface, and then the remaining solid reforms into the crystalline form. UW-Madison researchers have ...
New Capreomycin Derivatives for the Treatment of Multidrug-Resistant Tuberculosis
Organization: Wisconsin Alumni Research Foundation (WARF)
In recent years, multidrug-resistant forms of tuberculosis (MDR-TB) have become widespread. Because MDR-TB does not respond to first-line drugs such as isoniazid or rifampicin, second-line drugs such as capreomycin are increasingly being used. Capreomycins are particularly promising because they are the only drugs that are bactericidal against non-replicating Mycobacterium tuberculosis, the causative agent of tuberculosis. This suggests that they could be used to treat latent tuberculosis infections, in addition to active infections. ...
Muc16 Bound to Immune Cells Provides an Improved Indicator for Ovarian Cancer and Preeclampsia
Organization: Wisconsin Alumni Research Foundation (WARF)
Each year, approximately 20,000 American women are diagnosed with ovarian cancer and about 15,000 women die of the disease. The overall five-year relative survival rate for women with ovarian cancer is 46 percent. The survival rate improves to 93 percent if the cancer is diagnosed at an early stage, before it has spread. But only 19 percent of ovarian cancer cases are diagnosed at this local stage. CA125 currently is used as a biomarker for ovarian cancer. Levels of CA125 in the serum rise when a patient has ovarian ...
Influenza B Viruses with Reduced Sensitivity to Neuraminidase Inhibitors
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza is a major human disease caused by one of three types of influenza viruses. Type A viruses cause the most severe illnesses and are responsible for most epidemics; type B viruses generally cause less severe illnesses; and type C viruses result in mild respiratory illnesses and are not believed to cause epidemics. Because neuraminidase (NA) is critical for influenza virus infection, NA inhibitors, such as oseltamivir or zanamivir, are used to treat this disease. However, some strains of influenza have become resistant to these ...
Universal Nucleotidyltransferases Expand Sugar Substrate Families Available for Glycorandomization
Organization: Wisconsin Alumni Research Foundation (WARF)
Many of the compounds used in drug discovery by pharmaceutical companies are glycosylated, bacterial secondary metabolites. A glycosylated metabolite consists of a central core structure (aglycon) and various sugar (glycosyl) attachments. Because the sugar moieties of many of these metabolites define their biological activities, altering the carbohydrate ligands can lead to valuable new pharmaceuticals. A UW-Madison researcher previously developed a glycorandomization method for rapidly generating a diverse library of novel ...
Synthetic Ligands Capable of Strongly Inhibiting or Inducing Quorum Sensing in Bacteria
Organization: Wisconsin Alumni Research Foundation (WARF)
Quorum sensing is a process used by some bacteria to coordinate behavior based on local population density. To communicate, bacteria release signaling molecules, including low molecular weight ligands like acyl-homoserine lactones (AHL), into the environment. When a certain number of signaling molecules accumulates and the population reaches a sufficient density, the bacteria change their behavior to work together for a common goal. For example, they may adapt to the nutrients that are currently available, defend against other microorganisms ...
Sensitive Assay for Detecting Botulinum Neurotoxin, Neutralizing Antibodies or Inhibitors
Organization: Wisconsin Alumni Research Foundation (WARF)
Botulinum toxin is used for cosmetic procedures and to treat neurological disorders from spasmodic disorders to chronic pain syndromes. The most widely used form of botulinum toxin is the serotype A complex known as BOTOX. A single administration of BOTOX generally remains effective for four to five months before another dose is needed. However, many individuals develop immunity to the toxin after repeat dosing, making the injections less effective. To determine if an individual has developed neutralizing antibodies to ...
Biosynthetic Gene Cluster That Produces the Natural Antibiotics Platensimycin and Platencin
Organization: Wisconsin Alumni Research Foundation (WARF)
As the incidence of antibiotic resistance among bacteria continues to rise, the discovery of new antibacterial compounds has become increasingly critical to fighting infectious disease. According to the Food and Drug Administration, approximately 70 percent of bacteria that cause infections in hospitals are resistant to at least one of the drugs commonly used to treat infections. New types of antibacterial compounds are needed. Two potential antibiotics, platensimycin and platencin, are produced by the bacteria Streptomyces platensis. These ...
Novel Antibacterial Small Molecules
Organization: Wisconsin Alumni Research Foundation (WARF)
As the incidence of antibiotic resistance among bacteria continues to rise, the discovery of new antibacterial compounds has become increasingly critical to fighting infectious disease. According to the Food and Drug Administration, approximately 70 percent of bacteria that cause infections in hospitals are resistant to at least one of the drugs commonly used to treat infections. Methicillin-resistant Staphylococcus aureus (MRSA) is a particularly worrisome example. Some bacteria are resistant to all approved antibiotics and must be treated ...
High Throughput Assay for Sugar-Mediated Drug Transport
Organization: Wisconsin Alumni Research Foundation (WARF)
Because many anti-cancer drugs cause adverse side effects, molecular targeting techniques have been developed to specifically target drugs to tumor sites, minimizing their effects on healthy tissue. These techniques work by conjugating a small molecule or macromolecule to a cancer therapeutic. The small molecule or macromolecule then directs the therapeutic to the target site. Molecular targeting techniques offer a broadly applicable platform for modulating the selectivity, specificity and other characteristics of a wide range of anti-cancer ...
Diet-Based Agent for Treating Androgen-Dependent Prostate Cancer
Organization: Wisconsin Alumni Research Foundation (WARF)
Prostate cancer is the most common cancer among men in the United States. Like many other cancers, prostate cancer often can be treated successfully if it is diagnosed at an early stage. However, the standard treatment, surgery to remove the prostate and nearby lymph nodes, can result in impotence or incontinence. Less invasive treatment options are needed. One potential treatment is a diet-based agent, such as fisetin. Fisetin is a flavanoid found in many fruits and vegetables, including strawberries, apples and onions. Previous studies ...
Methods for Identifying Agents That Regulate Chromosomal Stability, Gene Activation and Aging
Organization: Wisconsin Alumni Research Foundation (WARF)
Histones are proteins around which DNA is wound. Because changes in histone acetylation affect how tightly the DNA is wound, thereby promoting or inhibiting DNA transcription, histone acetylation plays a role in physiological processes and disease states ranging from aging to cancer. The level of acetylation is controlled by histone acetyltransferases and deacetylases, such as the highly conserved sirtuins, which are encoded by silent information regulator 2 (SIR2) genes. In addition to histone proteins, recent evidence indicates that SIR2 ...
Peptide Mimotypes Bind Natural Antibodies, Modulate Autoimmunity
Organization: Wisconsin Alumni Research Foundation (WARF)
Naturally occurring antibodies are important components of the innate immune system. They participate in clearing pathogens, enhancing immune responses and preventing autoimmunity. The molecular recognition mechanisms underlying the functions of natural antibodies are poorly understood, largely because most monoclonal natural antibodies are polyspecific and recognize a variety of antigens that share no obvious structural similarity. This polyspecificity is likely an inherent property of natural antibodies that enables a ...
PAPSS1 – A New Treatment Target for HIV Infection
Organization: Wisconsin Alumni Research Foundation (WARF)
According to the Centers for Disease Control and Prevention, more than one million Americans may be infected with human immunodeficiency virus (HIV), which causes AIDS. While some treatments for HIV infection are available, there is no cure, and the virus can rapidly mutate and become resistant to current treatments. To develop additional therapies, more knowledge is needed about the factors that contribute to the life cycle of this retrovirus. Many of the cellular proteins involved in the late stages of the HIV life cycle have been ...
Strong, Stable, Semisynthetic Collagen Mimic for Wound Healing, Artificial Skin, Sutures and Leather
Organization: Wisconsin Alumni Research Foundation (WARF)
Collagen is the most abundant protein in vertebrates. It serves as the fundamental structural protein for vertebrate tissues and is critically important in wound healing. Many diseases, including arthritis, atherosclerosis, rheumatism, osteoporosis and osteogenesis imperfecta, are linked to weak or abnormal collagen. In addition to treating diseases associated with collagen abnormalities, collagen could be used for other medical purposes, such as healing wounds. It also can serve as a substrate for several types of artificial skin and as ...
Novel Peptide Adjuvant Improves Response to Influenza Vaccination
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza causes widespread morbidity and mortality worldwide. High-risk populations are routinely vaccinated in the United States, but influenza is still responsible for approximately 200,000 hospitalizations and 36,000 American deaths each year. The avian influenza A virus strain H5N1 is likely to be the cause of the next global influenza pandemic. Because this virus contains an antigen subtype that generally produces a poor immunogenic response in humans, more than one dose of vaccine may be needed to provide immunity. Influenza virus ...
Novel Antiviral Peptides Against Influenza Virus
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza viruses cause morbidity and mortality worldwide. In the United States, influenza is responsible for approximately 200,000 hospitalizations and 36,000 deaths each year. Two classes of antiviral drugs are currently approved to treat influenza. Adamantine derivatives prevent the virus from uncoating and releasing its genetic material into a cell. Neuraminidase inhibitors, on the other hand, prevent virus particles from leaving infected host cells and infecting new cells. However, viruses that are resistant to both classes of ...
Novel UGM Inhibitors for the Treatment of Tuberculosis and Other Microbial Infections
Organization: Wisconsin Alumni Research Foundation (WARF)
Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for eight million human infections and two million deaths worldwide each year. M. tuberculosis infections can be treated by antibiotics, but strains that are resistant to most or all known antibiotics are becoming widespread. To combat this resistance, novel targets for anti-microbial drugs are needed. An enzyme known as uridine 5`-diphospate (UDP) galactopyranose mutase, or UGM, is one such target. UGM plays a key role in the formation of UDP-galactofuranose ...
Novel Charge Shifting Anionic Polymers for the Controlled Release of Cationic Agents from Surfaces
Organization: Wisconsin Alumni Research Foundation (WARF)
The ability to deliver biomolecules, such as proteins or nucleic acids, into cells has many therapeutic and research applications. Polyelectrolyte multilayers (PEMs) have been used to deliver biomolecules into cells. PEMs essentially are thin plastic films with alternating layers of negatively charged (anionic) and positively charged (cationic) polymeric coatings. Biomolecules, such as nucleic acids, can be integrated into PEMs, which can be designed to controllably dissolve under physiologically relevant conditions to release the ...
More Complex-Type Retroviruses with Mixed Type LTR
Organization: Wisconsin Alumni Research Foundation (WARF)
The simpler retroviruses, such as spleen necrosis virus (SNV) and murine leukemia virus (MLV), cause disease in non-mammalian hosts. The more complex retroviruses, such as bovine leukemia virus (BLV), human immunodeficiency virus (HIV), human T-lymphotropic virus type I (HTLV-I) and human spumaretrovirus, cause prevalent diseases in mammalian hosts, including hoofed animals, primates, and humans. The more complex retroviruses create a challenge for vaccine development. Their retroviral proteins interfere with the host immune response ...
Antigenic Peptides of <i>Chlamydia trachomatis</i>
Organization: Wisconsin Alumni Research Foundation (WARF)
New reagents and vaccines are needed to diagnose and treat patients infected with Chlamydia trachomatis, a major human pathogen. The major outer membrane protein (MOMP) accounts for over 60 percent of the outer membrane protein synthesized during chlamydial development within infected cells. MOMP is highly immunogenic in humans, eliciting diverse antibody and T cell responses. However, preparing MOMP from chlamydiae is impractical and the extreme hydrophobicity of recombinant MOMP makes it hard to work with. Short antigenic MOMP peptides ...
Cytoskeletal-Active Agents for Glaucoma Therapy
Organization: Wisconsin Alumni Research Foundation (WARF)
Glaucoma is the second leading cause of visual impairment and the fourth leading cause of blindness in the United States. Although several therapies for glaucoma currently exist, these can be inconvenient (e.g., need to be applied several times daily), uncomfortable for patients to use and have unwanted systemic effects. UW–Madison researchers have developed a new pharmacological treatment for glaucoma. The treatment consists of an ophthalmic preparation of a non-corneotoxic serine-threonine kinase inhibitor such as H-7, ...
Treatment of Arthritic Disease
Organization: Wisconsin Alumni Research Foundation (WARF)
One of the most intensively studied arthritic diseases is rheumatoid arthritis, which affects more than one million adults in the U.S. Rheumatoid arthritis is a chronic and destructive disease that primarily affects the joints of the extremities and is characterized by inflammation of the synovium and destruction of joint structural components. The symptoms and morphology suggest a local immune response. Analogs of the hormonally active form of vitamin D, known as calcitriol or 1,25-dihydroxyvitamin D3, may modulate immunity in addition to ...
Novel Transglutaminase Improves Wound Healing
Organization: Wisconsin Alumni Research Foundation (WARF)
Transglutaminases, a family of cross-linking protein enzymes that serve as “biological glues,” are used to add texture to processed foods like meat and cheese, and also to repair surgical wounds, fractures and cartilage lesions. UW-Madison researchers have identified a novel transglutaminase, known as transglutaminase 5 (TG5). Because TG5 is expressed in epidermal cells, this transglutaminase could be used in wound dressings to speed healing. TG5 can also act as a G protein and may play a role in cell signaling, making it a ...
Long-Lasting Chimeric Botulinal Toxins
Organization: Wisconsin Alumni Research Foundation (WARF)
Botulinum toxin is used for the treatment of involuntary muscle movements, pain, spasticity and other neurologic disorders. However, each injection provides only temporary relief, necessitating periodic injections. UW–Madison researchers have developed a chimeric toxin comprising a botulinal neurotoxin heavy chain and nonclostridial toxin chain. The chimeric toxin has a longer lasting effect, reducing side effects and frequency of treatment.
Diagnosing Asthma Patients Predisposed to Adverse Beta-Agonist Reactions
Organization: Wisconsin Alumni Research Foundation (WARF)
Inhaled beta-agonists are the most commonly prescribed asthma treatments. The benefits of beta-agonists include relaxation of smooth muscles of the bronchial airways, increased ciliary beat frequency and reduced mucousal viscosity. However, reports of a possible association between the administration of beta-agonists and increased morbidity have raised safety issues. UW-Madison researchers have developed a method to identify asthmatics carrying a certain allele of the beta2-adrenergic receptor gene who are more likely to show a negative ...
System for Assaying Modulators of Procollagen Maturation
Organization: Wisconsin Alumni Research Foundation (WARF)
Modulating the kinetics of collagen deposition would be beneficial in applications such as wound healing. One mechanism for doing so is to use agents that alter the activities of two procollagen-cleaving enzymes, procollagen C-proteinase (PCP) and procollagen N-proteinase (PNP). However, no effective system now exists for assaying the effects of agents on PCP and PNP. UW-Madison researchers have developed a convenient cellular system for evaluating potential modulators of procollagen maturation – the cleaving of procollagen to ...
Mammalian Tolloid-Like Gene and Protein
Organization: Wisconsin Alumni Research Foundation (WARF)
Bone formation in mammals is governed by a set of bone morphogenetic proteins. Six of these proteins belong to the TGF-beta super family, while the seventh, bone morphogenetic protein 1 (BMP-1), belongs to the BMP-1 gene family. The mammalian BMP-1 gene encodes both the BMP-1 protein and the mammalian tolloid (mTld) protein on two distinct, alternately spliced mRNAs. UW-Madison researchers have developed a mammalian gene encoding a novel tolloid-like protein (mTll). mTll is distinct from the human and murine genes that encode BMP-1/mTld. It ...
Stable Collagen for Wound Healing, Artificial Skin, Sutures and Treating Collagen Disorders
Organization: Wisconsin Alumni Research Foundation (WARF)
Collagen is the most abundant protein in vertebrates. It serves as the fundamental structural protein for vertebrate tissues and is critically important in wound healing. Many diseases, including arthritis, atherosclerosis, rheumatism, osteoporosis and osteogenesis imperfecta, are linked to weak or abnormal collagen. In addition to treating diseases associated with collagen abnormalities, collagen could be used for other medical purposes, such as healing wounds. It also can serve as a substrate for several types of artificial skin and as ...
Method of Sensitizing Microbial Cells to Antimicrobial Compounds
Organization: Wisconsin Alumni Research Foundation (WARF)
Levels of antibiotic-resistant microbial organisms are increasing. The major mechanism of microbial resistance is decreased cell permeability, which includes the use of active drug efflux systems. Currently, the pharmaceutical industry combats the problem of antibiotic resistance by searching for new compounds that inhibit microorganisms. However, this approach does not address the underlying problem of altered permeability or the increased efflux capabilities of these organisms. UW-Madison researchers have developed a method for increasing ...
Method of Reducing Retinal Ganglion Cell Degeneration
Organization: Wisconsin Alumni Research Foundation (WARF)
Glaucomatous optic neuropathy is the second leading cause of permanent blindness in the United States, and is associated with an increased rate of retinal ganglion cell death. Treatment strategies have been directed exclusively toward reducing IOP (intraocular pressure), but are less effective in treating patients who do not respond to IOP-lowering drugs or surgery, or who suffer serious side effects from the therapy. A UW-Madison researcher has developed a method for reducing retinal ganglion cell death in glaucoma. The ...
Method of Suppressing Tumor Growth with Combinations of Isoprenoids and Statins
Organization: Wisconsin Alumni Research Foundation (WARF)
Mevalonate pathway-derived isoprenoids, found naturally in certain foods, suppress chemically-initiated carcinogenesis due to their antioxidant activity and induction of detoxifying activities. They can also suppress, via post-transcriptional actions, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, the rate-limiting activity in the synthesis of cholesterol from mevalonate. As a result of this suppression, the processing of tumor growth-associated proteins by intermediates along the mevalonate pathway is decreased. ...
The C-myc Coding Region Determinant Binding Protein (CRD-BP) and Its Nucleic Acid Sequence
Organization: Wisconsin Alumni Research Foundation (WARF)
C-myc protein levels influence cell proliferation, differentiation, and neoplastic transformation. Not surprisingly, given c-myc's roles in normal cell function, c-myc over-expression has also been found to play a role in tumor formation in experimental models and in human patients. A UW-Madison researcher has identified a coding region determinant binding protein (CRD-BP) that stabilizes c-myc mRNA by binding to the coding region determinant (CRD) on c-myc, thereby increasing the abundance of c-myc protein. Several properties of the CRD-BP ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Phospholipase A2 (PLA2) is an important enzyme in a pathway leading to inflammation, including the chronic inflammation experienced by many patients with lung disease. Patients with lung disease have reduced amounts of annexins, a group of calcium-dependent, phospholipid-binding proteins. In addition, there is a PLA2 stimulator in the respiratory secretions of patients with inflamed lungs. A UW-Madison resesarcher has developed methods for inhibiting PLA2 and suppressing the activity of a PLA2 stimulator to reduce lung inflammation. The ...
Use of Vitamin D Compounds to Prevent Transplant Rejection
Organization: Wisconsin Alumni Research Foundation (WARF)
Transplant rejection occurs when a transplant recipient's immune system attacks a transplanted organ or tissue. Immunosuppressive agents are given to transplant recipients to minimize rejection; however, many immunosuppressive agents have adverse side effects. New therapeutics that minimize transplant rejection are needed. UW-Madison researchers have developed a method of moderating transplant rejection in a transplant recipient by treating the patient with a vitamin D compound or analog, preferably 1,25(OH)2D3, to allow the acceptance of ...
Matrix Metalloproteinase Inhibitors and Method of Use
Organization: Wisconsin Alumni Research Foundation (WARF)
Matrix metalloproteinases (MMPs) are important biological targets in cancer therapy and in immunological diseases, playing a role in cell invasion, metastasis and inflammation. There remains, however, a need for effective, non-toxic compounds that are specific and potent inhibitors of MMPs. Many inhibitors are cytotoxic or difficult to synthesize, having limited in vivo application. UW-Madison researchers have developed solid phase methodologies to construct diversified combinatorial libraries of potentially clinically important MMP ...
Using Conjugated Linoleic Acid to Inhibit Cyclooxygenase-2 and Reduce Inflammation
Organization: Wisconsin Alumni Research Foundation (WARF)
Prostaglandins, lipid compounds derived from fatty acids, can induce painful inflammatory reactions. Inhibiting prostaglandin biosynthesis reduces inflammation. Most non-steroidal anti-inflammatory drugs, including aspirin, inhibit prostaglandin synthesis by inhibiting cyclooxygenase (COX), a key enzyme in the human body. This enzyme exists in at least two forms: COX-1 and COX-2. Drugs traditionally used for inhibition of COX often inhibit both forms and have been associated with intestinal ulceration. Selective COX-2 inhibitors have been ...
Mammalian Tolloid-Like Gene and Protein
Organization: Wisconsin Alumni Research Foundation (WARF)
Bone formation in mammals is governed by a set of bone morphogenetic proteins (BMPs). One member of the BMP subfamily is a novel mammalian tolloid-like gene and gene product (mTll-2). UW-Madison researchers have discovered the DNA and polypeptide sequences of this tolloid-like gene product, which is involved in the deposition of the extracellular matrix (e.g., osteogenesis) in vertebrates. mTll-2 is expressed at the highest levels in the developing heart of infants and in soft tissues of adults. Polynucleotides encoding mTll-2 can be ...
Organization: Wisconsin Alumni Research Foundation (WARF)
The incidence of sexually-transmitted diseases is in the millions. Chlamydia trachomatis (Ct) is an intracellular bacterium that is the leading cause of preventable infectious blindness (ocular trachoma) and of sexually transmitted diseases. Certain clusters of T cell epitopes in the major outer membrane protein (MOMP) of Ct may be promising candidates for inclusion in anti-Ct vaccines. Therefore, these peptides, and the DNA that express them, are suitable for subunit vaccines. Activation of CTLs requires specific recognition of ...
C-linked Analogs of N-(4-hydroxyphenyl) Retinamide
Organization: Wisconsin Alumni Research Foundation (WARF)
Retinoids have shown anti-tumor effects in preclincal models and represent a promising class of chemopreventive or chemotherapeutic agents. However, their utility has been limited by their narrow therapeutic indices. N-(4-hydroxyphenyl)retinamide (4-HPR) was developed as a less toxic analog of the vitamin A metabolite all-trans retinoic acid. 4-HPR has been shown to be active in numerous preclinical cancer models including mammary, bladder, lung, ovary, cervix, neuroblastoma, leukemia and prostate. However, 4-HPR can be hydrolyzed to ...
Recombinant Influenza Viruses for Vaccines and Gene Therapy
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza viruses show strong potential as vaccine and gene delivery vectors: they do not replicate through DNA intermediates (which may incorporate into the host genome); they elicit strong immune responses; and they exist in a wide range of antigenic variants, allowing repeated immunization and long-term use. However, influenza viruses have proven difficult to manipulate in the laboratory. As negative strand RNA viruses with viral RNA (vRNA) complementary to messenger RNA (mRNA), their replication requires a complex unit composed of viral ...
Anti-Anxiety Pharmaceuticals with Reduced Side Effects
Organization: Wisconsin Alumni Research Foundation (WARF)
According to the National Institute of Mental Health, anxiety disorders affect approximately 40 million American adults. These chronic illnesses can severely decrease a patient’s quality of life. Anti-anxiety drugs, called anxiolytics, are used to treat central nervous system disorders, including anxiety disorders. The most frequently prescribed class of anxiolytics is benzodiazepines. This class of pharmaceuticals includes Valium, Xanax and others. These drugs reduce anxiety by binding to inhibitory neurotransmitters called gamma ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Benzodiazepines like Valium and Xanax are commonly used as anxiolytics (anti-anxiety medications) and anticonvulsants. They bind to neurotransmitter receptors, particularly gamma-aminobutyric acid (GABA) type A receptors. However, benzodiazepines can cause significant side effects, including drowsiness, dizziness, impaired memory and decreased coordination. They can also lead to tolerance, dependence and abuse. Other anxiolytics, such as serotonergic agents, were developed to provide reduce side effects, but they have other drawbacks. ...
New Therapeutics for Alzheimer’s Disease and Memory Disorders
Organization: Wisconsin Alumni Research Foundation (WARF)
According to the Alzheimer’s Foundation of America, an estimated 5.1 million Americans have Alzheimer's disease and associated dementia. As the U.S. population ages, increasing numbers of people will be afflicted with dementia. Currently, there are only five approved drugs on the market to treat dementia, none of which are particularly effective. To address this major unmet medical need, researchers at UW-Milwaukee have developed new benzodiazepine derivatives that may be useful in the treatment of Alzheimer’s disease, Huntington’s disease, ...
Compounds Related to Capsaicin; Potential New Analgesic Agents
Organization: Wisconsin Alumni Research Foundation (WARF)
Capsaicin, a member of the vanilloid class of compounds, is the irritant compound in hot peppers. Capsaicin derivatives, along with TRPV1, a specific receptor for vanilloids, are an exciting area of research in the analgesic field. This biological material provides four new capsaicin derivatives. These compounds were rationally engineered to include modifications likely to affect TRPV1 receptor response.
Glycosylated Warfarin Analogs for the Treatment of Cancer
Organization: Wisconsin Alumni Research Foundation (WARF)
Warfarin is a synthetic analog of the natural anti-coagulant dicumarol. It has been used extensively as a rodenticide and as an anti-coagulant for human use. Recent studies have shown that some anti-coagulants can prolong the survival of cancer patients, suggesting that analogs of warfarin with novel or improved biological properties may be useful in developing new cancer therapeutics. Adding or changing the sugars that are attached to known compounds can improve the compounds’ pharmacological properties. Glycorandomization (see WARF ...
ADRB2 Gene Polymorphism Associated with Intraocular Pressure Response to Topical Beta-Blockers
Organization: Wisconsin Alumni Research Foundation (WARF)
An estimated 3 million people in the United States have glaucoma, a progressive optic neuropathy, characterized by increasing interocular pressure (IOP) that damages the optic nerve and can lead to blindness. The associated annual healthcare costs for glaucoma are estimated at $1.5 billion. Treatment options typically start with medications and progress to surgery, or a combination thereof. Medication options are numerous; in most cases topical beta-blockers represent the least expensive option to reduce IOP. There is a need, however, to ...
Modulating Atherosclerosis by Inducing Tolerance to Collagen V
Organization: Wisconsin Alumni Research Foundation (WARF)
Approximately 4.6 million people in the United States suffer from atherosclerosis, a chronic inflammatory disease characterized by deposits, or plaques, on the walls of the arteries. The plaques can rupture, setting into motion a process that culminates in blood clots associated with gangrene, heart attack and stroke. Autoimmune responses to local antigens are important components of the pathogenesis of atherosclerosis. In addition, individuals with autoimmune diseases such as rheumatoid arthritis or systemic lupus ...
Protein Receptors for Botulinum Neurotoxin E (BoNT/E) Enable Means of Reducing BoNT/E Toxicity
Organization: Wisconsin Alumni Research Foundation (WARF)
Botulinum neurotoxins (BoNTs), the most potent toxins known, are among the most dangerous potential bioterrorism threats. They cause botulism, a severe disease that can cause paralysis in humans and animals by blocking the release of neurotransmitters. The protein receptors for three of the seven BoNT serotypes, BoNT/A, B and G, have been identified. Identifying the receptor for BoNT/E, the third most important commercial serotype, would be useful for designing molecules that reduce or completely inhibit its ...
Treating Alexander Disease by Reducing Expression of Glial Fibrilary Acidic Protein (GFAP)
Organization: Wisconsin Alumni Research Foundation (WARF)
Alexander disease is an uncommon but fatal central nervous system disorder. This disease usually affects children and results in seizures, spasticity, hydrocephalus and psychomotor developmental delay. No cure exists and no standard treatment has been developed. Most patients with Alexander disease have mutations in the gene for glial fibrilary acidic protein, or GFAP, which is the major structural protein in astrocytes. The GFAP mutations occur within an amino acid sequence that is highly conserved among intermediate filament proteins. ...
Sigma 1 Receptor Inhibitors May Provide New Cancer, Psychosis, Addiction and Other Therapies
Organization: Wisconsin Alumni Research Foundation (WARF)
The sigma 1 receptor is an intracellular molecule that shares no known homology with any mammalian proteins. In the brain, sigma 1 receptors regulate the activity of ion channels via protein-protein interactions. The activation of sigma 1 receptors may promote neuronal differentiation and interfere with programmed cell death, potentially leading to cancer. The sigma 1 receptor also has been implicated in other disorders, including psychosis, drug addiction and retinal degeneration. As a result, ligands for this receptor may provide a new ...
Polyethylene Glycol (PEG) Micelles with Cholesterol Provide an Improved Delivery System for AmB
Organization: Wisconsin Alumni Research Foundation (WARF)
Systemic fungal infections are a significant and often life-threatening clinical problem, particularly in patients with a suppressed immune system. The drug of choice for treating these infections is Amphotericin B (AmB), a broad spectrum antifungal agent that acts by disrupting fungal cell walls. But AmB is extremely toxic, poorly soluble in water and difficult to formulate and administer. UW-Madison researchers previously demonstrated that AmB could be made soluble and deaggregated by PEG-DSPE micelles, resulting in substantial reduction in ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Redox-dependent signaling of cell death is a final pathway common to many conditions and diseases, including several neurodegenerative disorders and ophthalmological disorders like glaucoma. Protecting cells from downstream oxidative signaling of cell death could provide a method for preventing or treating these disorders. This cell death pathway also is common to tissue injured by radiation. Relatively few available treatments are radioprotective, i.e., they are effective when administered at or before the time of radiation ...
Using Anti-Estrogens to Treat Cervical or Vaginal Cancer and Dysplasia
Organization: Wisconsin Alumni Research Foundation (WARF)
More than 11,000 American women were diagnosed with cervical cancer in 2008. Treatment of this disease, which consists of surgical, chemotherapeutic and radiation therapies, costs an estimated $1.7 billion each year. And current therapeutic approaches have five-year survival rates of less than 50 percent worldwide. Human papillomaviruses (HPVs) are small DNA viruses that are associated with almost all cervical cancers. Vaccines against HPV have been developed, but their long-term effects and ability to prevent cervical cancer are unknown. ...
Novel Peptide Therapeutics for Bone Regeneration
Organization: WORLDiscoveries - University of Western Ontario
The present invention comprises a suite of proprietary collagen-binding peptides derived from bone sialoprotein (BSP) that are effective in promoting bone repair and regeneration. Researchers at the University of Western Ontario have identified BSP peptide sequences responsible for the nucleation of bone mineral crystals and were also able to pinpoint the region that mediates tight and specific binding to collagen, the structural protein of bone. Such collagen binding peptides are clinically valuable, as they could be used effectively as ...
Rapid Optimization of Dose Distribution for Radiation Treatment (FIDO)
Organization: WORLDiscoveries - University of Western Ontario
Fast Inverse Dose Optimization (FIDO) is an algorithm and associated software that does not rely on the current “trial and error” search to find the optimal radiation beam plan for a patient, but instead solves a single algebraic procedure directly. As a result, FIDO delivers an optimal treatment plan in seconds rather than the current standard of minutes to hours (e.g. the TomoTherapy Inc. system uses 32 computers to develop a treatment plan and it can still take overnight for complex plans). Thus, FIDO eliminates the need to ...
Organization: STC UNM
Researchers at the University of New Mexico have developed a novel method to significantly decrease the regulatory measures to tag dosages. This method allows the identification and detection of counterfeit drug products using internal coding of drug dosage forms and thus allowing for the detection of counterfeit products.
Hydrogel Particles for Drug Delivery to the Lung
Organization: STC UNM
Improved swellable particles for drug delivery to the pulmonary system, and methods for their synthesis and administration.
Practical Synthesis of Chiral Dihydroquinazolinones
Organization: STC UNM
This technology has developed a novel method for creating a highly enantioselective aza-Henry reaction of ketimines using simple quinine-thiouea as catalyst with using a low as 1 mol% catalyst loading. A highly efficient H-bond mediated enantioselective addition of nitroalkanes to ketimines is achieved for the first time under mild reaction conditions in high yields.
Isotope Control of Drug Action
Organization: STC UNM
This novel technology describes a technique used for enhancing already existing drugs that goes a step further than current methods which reduce metabolism at hydrogen. Researchers at the University of New Mexico and Los Alamos National Laboratory have the ability to dial in and actively control drug action by using isotope effects to control free radical chemistry of drugs. This can be used to either increase a desired action to enhance therapy or to decrease an undesired, adverse reaction that may have toxic effects. Although this technique ...
Organization: Simon Fraser University
This invention relates to the production and characterization of a mutant strain of Aspergillus fumigatus, a method for inhibiting siderophore biosynthesis in the fungi, and an assay for identifying drug candidates having potential inhibitory activity. The invention will be particularly useful in the discovery of drugs for immunocompromised patients susceptible to infections caused by Aspergillus fumigatus, such as pulmonary aspergillosis.
Novel Therapeutic Approach to the Prevention and Treatment of Staphylococcus Aureus Infections
Organization: WORLDiscoveries - University of Western Ontario
The present technology suite is based on the identification of a suite of highly specific, proprietary bacterial drug targets in staphylococcus aureus, that can be used individually or as a group to develop small molecule or peptide drug leads with powerful anti-infectives properties. The underlying mechanism of action is to inhibit bacterial iron uptake mechanisms and thus to starve the pathogen of its critical food source. One target (UWO-AE-008) is an iron-regulated, nine gene operon (sbn) whose products are involved in the synthesis of ...
Diagnostic System for Early Stage Osteoarthritis and Therapeutic Discovery
Organization: WORLDiscoveries - University of Western Ontario
The present invention relates to osteoarthritis (OA) and methods of OA diagnosis. The invention covers methods by which one might diagnose OA through differential expression profiling of chondrocyte-specific genes or proteins. The targets were identified using a genome-wide analysis of dysregulated genes in a specialized rat OA model that best models the human progression of the disease. The technology can manifest itself as a kit to diagnose OA using at least one probe directed to a chondrocyte-specific gene that exhibits differential ...
A non-invasive test of oocyte quality in assisted conception
Organization: WORLDiscoveries - University of Western Ontario
Western researchers have developed an innovative, real-time test of oocyte quality, applicable to assisted conception treatments, that does no harm to the oocyte itself. The present invention comprises a methodology to test strength of gap junctional coupling among follicular cells as a surrogate measurement of oocyte health. The invention is based on findings by Western researchers, that gap junctional coupling among follicle cells is a determinant of oocyte quality in humans. Since the follicle cells can easily be detached from the oocyte ...
Novel Bifunctional Cancer Drugs - Metnase and Intnase Inhibitors and Their Use in Treating Cancer
Organization: STC UNM
This invention presents novel cancer treatment compositions and associated therapeutic methods. Small chemical bifunctional inhibitors of DNA replication and repair protein Metnase and Intnase are introduced. A therapeutic method is also included that utilizes the inhibitors to increase the effectiveness of cancer treatment protocols.
Micro Fine, Dry Powder Pulmonary Drug Delivery Technology Suite
Organization: WORLDiscoveries - University of Western Ontario
Advancements in the development of ultra-fine drug molecules and peptides suitable for pulmonary delivery have created the requirement for novel handling, metering and drug dispensing techniques; while circumventing the problem of agglomeration (usually solved by mixing the active drug formula with excipients). The present technology suite is comprised of the following two inventions: Volumetric Metering of Small Quantity of Ultra Fine Powder From Fluidized Bed (Ref: UWO-AA-010): A novel fluidization bed design that can precisely ...
Bone Marrow Derived Cells that Stimulate Pancreatic Regeneration in Type II Diabetes
Organization: WORLDiscoveries - University of Western Ontario
The present invention relates to methods comprising of specialized mononuclear cells from bone marrow that can rescue hyperglycemia and augment pancreatic repair. The cells are distinguishable from classic circulating hematopoietic stem cells and stimulate the repair or regeneration of endogenous islet cells. They can be isolated directly from bone marrow and applied without culture in vitro. The cells do not themselves transform into islets but instead stimulate endogenous cells to re-enter the cell cycle and generate insulin producing ...
Protein Disulfide Isomerase Inhibitors for Inhibiting HIV Entry Into Cells
Organization: STC UNM
New PDI inhibitors have been characterized in vitro. Compounds that reverse and remove these PDI inhibitors are also described. These inactivating agents are applicable for the termination of toxicity that may occur as a result of treatment with a PDI inhibitor. Other biochemical studies are in progress. A proposal for design and evaluation of drug toxicity is available upon request.
Organization: WORLDiscoveries - University of Western Ontario
A Robarts’ Scientist has identified a target molecule that can serve as a switch between scar establishment and regenerative matrix deposition by astrocyte cells. By altering expression of this gene, one may disrupt the mechanism of chondroitin sulfate proteoglycan (CSPG) modification and simultaneously activate the expression and secretion of laminin and fibronectin in the scar, thus favouring regeneration following spinal cord injury or stroke. The system has been demonstrated to be valid in mouse models and serve function in human ...
Compounds For Binding to ERα/β and GPR30 to Treat Disease States or Conditions
Organization: STC UNM
Compounds specific for binding to estrogen receptors alpha/beta and GPR30 for use in treating disease states and conditions mediated through these receptors. Additionally, the present invention includes a method for identifying chemical compounds that interact with estrogen-related receptors alpha/beta and GPR30.
A Compound for the Maintenance of Prostate Health and the Treatment of Prostatic Disorders
Organization: STC UNM
A Novel compound that selectively decreases androgenic activity and growth of prostate cancer cells. Further, it has been shown to induce prostate cancer cell death. Its effectiveness has been indicated by epidemiology and cell studies. Our compound is non-steroidal and could be taken orally to prevent and halt prostate cancer.
Compound for Treatment of TB with Improved Activity over Isoniazid
Organization: STC UNM
A novel compound for treatment of TB showing improved activity over isoniazid. Initial testing has revealed that this proprietary compound, NM031, is 10 times more effective than isoniazid in the treatment of tuberculosis infection. The inventor, Dr. Graham Timmins was awarded the STC Gap Fund Award of $25,000 for development work related to this technology. His proposal aimed to deliver a pre-clinical, pre-IND package of information for the NM031 compound, and to show the effects of this compound on drug resistant strains ...
Dual target Inhibitors for Inhibiting Human Breast Cancer Cells' Growth
Organization: STC UNM
Curcumin and resveratrol analogs with anti-tumor activities have been developed by University of New Mexico researchers. Several analog libraries of these compounds were screened for their ability to inhibit glyoxylase-1 by a reporter-cell-based system and some of these were found to be comparable to and/or better than curcumin. The researchers discovered the additional ability of some of these analogs to prevent the activation of NF- κB and AP-1 thereby acting as dual/triple inhibitors of signaling, metabolic and glyoxylase-1 pathways.
Method for Regulation of Integrin Affinity and Cell Adhesion
Organization: STC UNM
Researchers at the University of New Mexico have developed a method of inhibition or reversing adhesion in a patient or subject in need by providing an effective amount of a nitric oxide/cGMP signaling pathway modulator compound. UNM’s finding that NO/cGMP pathway directly regulates integrin-dependent immune cell adhesion provides the rationale for repositioning of existing drugs toward pathologies, where integrin-mediated excessive immune cell adhesion/recruitment is envisioned to be detrimental.
Organization: University of Louisville
Intellectual Property U.S. Patent Issued; 6,551,998 B1. PCT Published; WO 00/78793 A2.
Organization: STC UNM
This novel invention utilizes a unique combination of virology and quantitative biophysical tools to identify small molecule inhibitors of pathogenic Hantaviruses. This technology has identified new small molecule inhibitors of hantavirus infection by blocking the very first step in the infection process, namely the binding of hantaviruses to their surface co-receptor decay accelearating factor (DAF).
Nanovectors for Treatment of Brain Cancer
Organization: Rice University
Novel Compositions and Methods for Inhibiting Viral and Bacterial Infections
Organization: STC UNM
Researchers at the University of New Mexico have identified an infection antagonist that inhibits infection of a HSPG-containing infection complex. Theses antagonists can inhibit binding and uptake of any microorganisms - whether viral or bacterial - that involve HSPG interactions prior to cellular uptake. Viable candidates to inhibit infection of: HPVs, HIV, Herpes viruses, Vaccinia, HCV and other Flaviviruses, Chlamydia
A Mechanical Patient Controlled Analgesia Device
Organization: STC UNM
A University of New Mexico researcher has developed a patient controlled analgesia device that allows a patient to safely titrate their own pain medication. This device is purely mechanical, low cost and disposable. It allows for emergency patients to safely titrate their own loading dose in a timely manner.
Ras-related GTPases as Targets of Small Molecule Inhibitors
Organization: STC UNM
Through a concerted and unbiased screen for small molecules, researchers at the University of New Mexico have identified novel and FDA approved inhibitors of Ras GTPases from the Molecular Libraries Screening Center Network. Using FDA approved drugs, they have demonstrated the ability to inhibit ovarian cancer cell proliferation and migration by inhibiting Ras superfamily GTPases, particularly the Rho family. Small GTPases play key regulatory roles in nearly all cellular pathways from cell signaling to cell growth control and ...
Organization: WORLDiscoveries - University of Western Ontario
A cardiovascular scientist at Robarts has identified a novel combination of growth factors that may serve as a basis for promoting blood vessel formation, and stabilizing those vessels whose stability may be compromised. The ability of these factors to support angiogenesis has been validated within in vitro and in vivo models. Similarly, this combination has been demonstrated to promote investment of premature blood vessels into fully reactive forms within in vivo models. Finally, preliminary results in mouse models demonstrate the ...
Target for the Diagnosis and Treatment of Osteoarthritis
Organization: WORLDiscoveries - University of Western Ontario
The present invention relates to a protein whose expression is upregulated in a rat model of osteoarthritis (OA), as well as in a subset of human patients with late stage OA. In vitro studies have confirmed that overexpression of this protein induces many features of OA including: 1) increased chondrocyte proliferation, 2) reduced anabolic activity in primary chondrocytes as evidenced by a reduction in the expression of aggrecan, type II collagen, and cartilage link protein, and 3) increased expression of catabolic and inflammatory mediator ...
A Secreted Therapeutic and Drug Discovery Target for Early Stage Osteoarthritis
Organization: WORLDiscoveries - University of Western Ontario
The present invention relates to a diagnostic and therapeutic secreted target protein that is upregulated in a subset of human patients with osteoarthritis (OA). The target also functionally correlates to OA in a rat model of the disease. In vitro studies have confirmed that overexpression of this target: 1) decreases the expression of procartilage extracellular matrix proteins ie. aggrecan, type II collagen, and cartilage link protein, 2) increases undesirable cell proliferation within the cartilage matrix, and 3) increases the production ...
Novel Drug Delivery System for Treatment of Cancer, Diabetes, and Other Diseases
Organization: NDSU Research Foundation
A series of fatty acid grafted copolymers of low molecular weight chitosan (LMWC) were synthesized via EDC mediated coupling reaction. These fatty acid grafted LMWC copolymers form cationic nano-micelles in an aqueous environment. Due to their positive charge, these polymeric micelles effectively condensed negatively-charged plasmid DNA (pDNA) through electrostatic interaction to form nanoscale polyplexes. These polyplexes demonstrated excellent pDNA binding ability and efficiently protected the pDNA from nuclease degradation.
Drug Delivery Vehicle for Treatment of Eye Disease: Glaucoma
Organization: NDSU Research Foundation
Human carbonic anhydrase (hCAII) is a metalloenzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate and is associated with glaucoma (a major cause of blindness). Carboxybenzenesulfonamide, an inhibitor of the hCAII enzyme, is attached to nanoceria particles using epichlorohydrin as an intermediate linkage. Along with the CA inhibitor, a fluorophore (carboxyfluorescein) is also attached on the nanoparticles to enable the tracking of the nanoparticles in vitro as well as in vivo. X-ray photoelectron spectroscopic ...
Increased Fertility via Novel Use of Lipoic Acid
Organization: NDSU Research Foundation
Lipoic acid is a naturally occurring compound that has been shown to modulate insulin sensitivity when supplemented to the diet. Elevated blood insulin concentrations have been shown to decrease progesterone catabolism in several species by modulating liver enzyme. The NDSU approach shows that the introduction of lipoic acid decreases progesterone (P4) catabolism by the liver, leading to an overall increase in fertility. During the NDSU research, ovariectomized ewes were fed an alfalfa-grass ration at 95% of ad libitum. One group of ewes was ...
Novel Method of Releasing Liposomal Drugs by a Cancer-Associated Enzyme
Organization: NDSU Research Foundation
The passive release of drugs and other molecules from liposomes is a slow process. The uniquely-formulated liposomes circumvent this problem by presenting on the surface triplehelical substrate peptides for MMP-9. In the presence of elevated levels of this enzyme (as found for cancer and arthritis patients), the peptides are cleaved rapidly, leading to the liposome destabilization and release of the encapsulated contents. The liposomal formulations are non-toxic to a variety of human cell lines.
Prophylactic, Therapeutic, and Diagnostic Remedy for Treatment of Colibacillosis Infection
Organization: NDSU Research Foundation
Pharmaceutical Intervention For Snoring And Other Motoneuronal-Related Neuromuscular Dysfunction
Organization: University of California, Los Angeles (UCLA)
Researchers at UCLA have identified a generic pharmaceutical compound that treats snoring, sleep apnea and other motoneuronal-related neuromuscular dysfunctions such as disorders of breathing movements and other bodily movements. The compound targets the genioglossus muscle that controls tongue movement and stiffness. Proper functioning of this muscle is critical for preventing partial or complete closure of the upper airway, which leads to snoring or apnea (absence of breathing) during sleep.
Organization: Rutgers University
Novel Chemotherapeutic Agents for Anti-Tumor and Anti-Cancer Drugs
Organization: NDSU Research Foundation
Organization: Health Research Inc
The flavivirus genome is a plus-sense,single-stranded RNA of about 11,000 nucleotides. The genomic RNA consists of a 5' untranslated region (UTR), a single open reading frame (ORF), and a 3' (UTR). The single ORF encodes a long polyprotein that is co-translationally processed by viral and host proteases into ten mature viral proteins. The N-terminus of the polyprotein contains three structural proteins: capsid (C), premembrane (prM/M), and envelope (E). The C-terminus of the polyprotein contains seven nonstructural (NS) proteins: NS1, NS2A, ...
Organization: University of Missouri Columbia
Inhibition of oxidosqualene cyclase has led to the induction of apoptosis in tumor cell lines and inhibition of tumor growth in xenograft models.
Pharmaceutical isomorph stabilization
Organization: University of Missouri Columbia
Recombineering Method for Improved Viral Therapies
Organization: University of Miami
HIV/AIDS is a worldwide problem affecting 33 million people, with over 2 million deaths per year. Management of AIDS involves combinations of three or more antiretroviral drugs, but because HIV has the ability to mutate, new drug-resistant strains may be produced, rendering the treatment ineffective. The study of viral proteins has been mostly limited to single clones and unable to detect the contribution of genomic variability to the overall virus phenotype. The present invention involves a method of rapidly obtaining viral recombinants ...
Small Molecules for Islet Expansion in the Treatment of Diabetes
Organization: University of California, Los Angeles (UCLA)
Dr. Anil Bushan and colleagues at UCLA have identified a number of small molecules capable of expanding pancreatic islet numbers. These compounds act through inhibition of a common molecular pathway. Currently, no small molecule based methods are available to expand islets in vitro or in vivo.
A Novel Method for Improving Sperm Motility in Infertile Men
Organization: University of Miami
Male infertility due to low sperm mobility occurs in up to 15% of the population. If there was a simple way to increase sperm motility it would be an extraordinary help to achieve pregnancy in couples with this problem. The motility of sperm is significantly increased by inactivating or reducing the biological activity of inflammatory cytokines present in the sample.
Synthesis of Homogenous Nanospheres with Diameters Less Than 100 nm
Organization: NDSU Research Foundation
This synthesis procedure utilizes ozone as an oxidant in the polymerization of pyrrole to produce polypyrrole nanospheres. The key inventive concept is that there are no template materials involved in the synthesis process and that this reaction is carried out in water at room temperature. The ozone reacts very quickly, which means there should be no harmful residue left behind in the nanospheres. The reaction produces well-defined, nanosized, spheres of polypyrrole with a narrow particle size distribution.
Novel Antichlorinergic Medications for Urinary Incontinence
Organization: Indiana Univ-Purdue University Indianapolis
This invention includes methods, chemical compounds, and pharmaceutical compositions and kits for the treatment of bladder incontinence by the administration of quaternary anticholinergics agents with prolonged duration of action directly to the bladder (intravesicle administration by catheter) to result in prolonged bladder control. Agents with durations of action between a week and a month could be useful for a significant number of patients and perhaps reach distinct groups for whom no satisfactory treatment is currently available.
Biocompatible Formulations of Poorly Soluble Anticancer Drugs Such as Gossypol
Organization: Wisconsin Alumni Research Foundation (WARF)
Many powerful drugs have only limited usefulness because they are relatively insoluble in aqueous solutions. For example, gossypol has been identified as an effective inhibitor of Bcl-2 proteins, which play a role in apoptosis, but is difficult to deliver to tumor sites in vivo because of its low solubility. In addition, many cancer treatment strategies have shifted to combination drug therapy. It's hoped that the ability to safely and simultaneously deliver multiple drugs to target several cancer-related pathways at one time will improve ...
BACE1 Inhibitors Reduce β-Amyloid Production, Provide Potential Treatment for Alzheimer’s Disease
Organization: Wisconsin Alumni Research Foundation (WARF)
Alzheimer’s disease is the most common form of dementia, affecting an estimated 27 million people worldwide. This disease has a large economic impact with estimated direct and indirect costs of $148 billion annually in the United States. Plaques composed of aggregated β-amyloid peptide, which accumulate in the brains of patients with Alzheimer’s disease, play a key role in the pathogenesis of the disease. β-amyloid is formed when the enzyme BACE1 cleaves the β-amyloid precursor protein. Because BACE1 is the rate-limiting step in β-amyloid ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Accurately reproducing the blood-brain barrier in an in vitro setting has been a longstanding challenge. Current methods require the independent isolation of multiple cell types, and the quality of these preparations varies. UW-Madison researchers have developed a simpler, more reproducible in vitro model of the blood-brain barrier. Most existing models include primary brain microvasculature endothelial cells (BMECs), which form the blood-brain barrier in vivo, and the corresponding primary astrocytes, which affect the barrier. The improved ...
New Antimicrobials for Treating Bacterial Infection and Contamination
Organization: Wisconsin Alumni Research Foundation (WARF)
The ability of bacteria to adapt and resist antibiotics has led to growing initiatives in the United States and other countries to develop new drugs and modify existing chemical structures to increase their efficacy. A promising strategy for antibiotic development is to disrupt the cellular machinery that bacteria use to divide. Once viewed as a simple process, bacterial cell division is now recognized to be a complex process that involves a large family of proteins that regulate the location and process of division. The protein machinery ...
Treating Pulmonary Disorders with Artificial Lung Surfactant
Organization: Wisconsin Alumni Research Foundation (WARF)
Lung surfactant (LS) is a lipid-protein mixture that coats the internal surface of the lungs. It reduces the work of breathing by helping to keep air sacs open and stable. Deficient or dysfunctional LS results in infant or acute respiratory distress syndromes (IRDS or ARDS, respectively). IRDS syndrome can be treated with pig- or bovine-derived surfactant replacements. But these substances are not ideal because they carry the risk of animal infection and are expensive to extract and process on a large scale. No such treatment exists for ...
Enhanced Engineering of the Methylerithritol and Mevalonate Pathways
Organization: Rice University
Vitamin D Analogs for Treating Bone Cancers and Diseases
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analog “CPA-1” for Treating and Preventing Deadliest Cancers
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analog “MDBE20” for Treating Obesity, Parathyroid Problems and Autoimmune Diseases
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analog “UW-05” for Skin Therapy, Parathyroid and Autoimmune Disease Treatment
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analog “DA2HE” to Treat and Prevent Polyps, Hyperplastic Intestinal Disorders
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Metabolic Regulation of Ovarian Cancer Cells through Pyruvate
Organization: Rice University
Process for In Vivo Plastid Protein Production
Organization: Rice University
Treating X-Linked Hypophosphatemia (XLH), Bone Deformity and Other Renal Phosphate Wasting Disorders
Organization: Wisconsin Alumni Research Foundation (WARF)
X-linked hypophosphatemia (XLH) is a genetic type of rickets/osteomalacia marked by progressively severe skeletal abnormalities and growth retardation. It is a renal phosphate wasting disorder, which involves defective phosphate transport due primarily to elevated circulating concentrations of FGF-23. Mutations in the PHEX gene underlie the genesis of XLH, which occurs in about 1:20,000 live births and can result in bone deformities, growth retardation and tooth abscesses. Therapy currently is limited to combination drug regimens, including ...
Safer Influenza Vaccine from Replication-Knock Out Virus
Organization: Wisconsin Alumni Research Foundation (WARF)
Influenza viruses instigate annual global epidemics. The first influenza pandemic in 40 years occurred during the 2009-2010 season, when a novel H1N1 strain emerged and spread worldwide. The United States alone witnessed an estimated 61 million cases and more than 12,000 deaths. Influenza can resist drugs and bodily defenses because it is prone to mutate. Vaccination is one of the most effective countermeasures. Two types are currently available. The ‘flu shot’ is an inactivated (killed) vaccine. It is considered safe but confers ...
Easier, More Flexible Synthesis of Therapeutic and Promising Compounds
Organization: Wisconsin Alumni Research Foundation (WARF)
Many pharmaceuticals and other biologically active molecules contain chemical sequences called triads that are challenging to prepare in the laboratory. Specifically, triads are three or more contiguous heteroatom-bearing carbons. These sequences are featured in useful compounds like the anti-influenza medicine Tamiflu, which relies on a unique Chinese evergreen and lengthy manufacturing process. The drug’s reliance on natural sources has led to supply shortages in the past. New methods clearly are needed for synthesizing these important ...
Crystallized Vitamin D Analog “F-24”
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Crystallized Vitamin D Analogs “MET-1” and “MET-2”
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Crystallized Vitamin D Analog “SAG-2”
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Crystallized Vitamin D Analog “24F2-DM”
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Crystallized Vitamin D Analog 2-Methylene-18,19-Dinor-1Alpha-Hydroxy-Homopregnacalciferol
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Systems and Methods for Diagnosis of Lawsonia Intracellularis
Organization: University of Kentucky
Lawsonia intracellularis is a pathogen that affects mammals, including horses and pigs. In horses, L. intracellularis causes equine proliferative enteropathy (EPE), the symptoms of which include anorexia, fever, lethargy, depression, peripheral edema, weight loss, colic, and diarrhea. Weanlings and young yearlings typically contract EPE in the fall and early winter, probably from injecting contaminated fecal matter. Diagnostics are available to detect L. intracellularis infections in pigs and rabbits. This invention can be used to detect ...
Novel strategies and drug repurposing for targeting Flaviviridae and HIV infectious virus production
Organization: Stanford University
Novel strategies and drug repurposing for targeting Flaviviridae and HIV infectious virus production
Organization: Stanford University
Efficient High-Throughput Screen for Identifying Novel Anti-Fungal Compounds
Organization: Louisiana State University Health Sciences Center New Orleans
An LSUHSC researcher has established a high-throughput screen for the identification of novel compounds that target the endolysosome/vacuole. This assay consists of two parts. The first is growing an indicator fungal strain that undergoes a phenotypic change when its vacuole is disrupted. The second is treating the indicator strain with a library of compounds and monitoring this phenotypic change. This assay serves as a screening platform that can be adapted to identify compounds that disrupt the mammalian lysosome.
Modified INSM1-Promoter for Neuroendocrine Tumor Therapy and Diagnostics
Organization: Louisiana State University Health Sciences Center New Orleans
Insulinoma-associated 1 (INSM1) is as a transcription factor that functions in many difference aspects of embryonic development, evidenced by the fact that it’s expression is restricted to early fetal development in neuronal and endocrine tissues and is absent in normal adult tissues. However, INSM1 is strongly expressed in neuroendocrine tumors, including small cell lung carcinoma (SCLC), medullablastoma, neuroblastoma, medullary thyroid carcinoma, insulinoma, retinoblastoma, pheochromocytoma, and pituitary tumors. The expression of ...
Methods and Compositions Containing MTOR Inhibitors for Enhancing Immune Response
Organization: Roswell Park Cancer Institute
The present invention provides compositions and methods for enhancing the efficacy of vaccines. In one embodiment, the invention provides a method for enhancing an immune response to an antigen in an individual. The method comprises administering to the individual the antigen and an mTOR inhibitor. The mTOR inhibitor and the antigen may or may not be administered as components of the same composition, and may be administered concurrently or sequentially. It is preferable to administer the mTOR inhibitor after administration of the antigen. ...
Methods and Compositions Using Peroxiredoxin 1 (PRX1) as an Adjuvant
Organization: Roswell Park Cancer Institute
The present invention provides compositions and methods for stimulating immune responses. The compositions comprise an antigen and isolated Prx1 protein. The antigen and the Prx1 protein can be provided in a complex, or they may be covalently linked to one another. The Prx1 protein in the complex can be present in a multimer. In one embodiment, the multimer is a decamer. The compositions may further comprise antigen presenting cells that have been exposed to the antigen and/or the Prx1 protein. The antigen can be any antigen against which ...
Methods and Compositions Containing Fc Fusion Proteins for Enhancing Immune Responses
Organization: Roswell Park Cancer Institute
The present invention provides compositions and methods for inhibiting growth of cells in an individual. The cells that are targeted by the compositions and methods of the invention express an antigen, a mimotope of the antigen, or a CXCR4 chemokine receptor. In one embodiment, the method comprises administering to the individual a composition comprising a polynucleotide encoding an immunoglobulin (Ig) Fc and an antigen expressed by the cells or a mimotope of the antigen. In another embodiment, the method comprises administering to the ...
Anti-endoglin Antibodies and Knockin Mice Expressing Novel Human/Mouse Chimeric Endoglin
Organization: Roswell Park Cancer Institute
The present invention provides compositions and methods that relate to prophylaxis and therapy of angiogenesis associated disease. The invention includes providing novel knockin mice which express novel human/mouse chimeric endoglin. The mice are useful for evaluation of the in vivo efficacy of anti-human endoglin mAbs which can be used in antiangiogenic therapy of human tumor angiogenesis and human angiogenesis-associated diseases characterized at least in part by excessive vascularization. In various embodiments, the endoglin gene of the ...
Therapeutic and Diagnostic Method for Ataxia Telangiectasia
Organization: Louisiana State University Health Sciences Center New Orleans
A researcher at LSUHSC in New Orleans identified novel therapeutic targets and biomarkers for the diagnosis and progression of Ataxia Telangiectasia (A-T), along with a system for identifying and testing compounds that may be used for the treatment of A-T. The underlying pathogenic mechanism of A-T is thought to largely be due to defects in DNA repair mechanisms; however, this researcher identified a novel pathway distinct of DNA repair that likely contributes to A-T. This research presents a unique opportunity to advance the diagnostic and ...
Vitamin D Analogs “1D-QM” and “1D-QMS” for Cancer, Bone Disease Therapy
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analogs “2EG” and “T-2EG-S” for Treating Cancer and Bone Disease
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
Vitamin D Analogs “3D-QM” and “3D-QMS” for Treating Cancer and Bone Diseases
Organization: Wisconsin Alumni Research Foundation (WARF)
The hormonally active form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, has shown promise for treating diseases ranging from osteoporosis to cancer to psoriasis. However, the hormone mobilizes calcium from bones and increases intestinal absorption of dietary calcium. Effective therapeutic concentrations can lead to hypercalcemia; a condition characterized by elevated blood calcium levels, alterations in mental status, muscle weakness and calcification of soft tissues and organs such as the heart and kidneys. Therefore, a ...
New Drugs for Malaria and Bacterial Infections
Organization: University of Illinois, Urbana-Champaign
Two-Component Lantibiotic, Lacticin 3147
Organization: University of Illinois, Urbana-Champaign
Organization: University of Illinois, Urbana-Champaign
Genes for the Biosynthesis of Plantazolicin, a Molecule Effective in Killing Bacillus Anthracis
Organization: University of Illinois, Urbana-Champaign
Microcins are antibacterial peptides that differ from popular broad-range antibiotics in a variety of ways. One important difference is that microcins target a narrow spectrum of bacteria. As a result, natural human microbial flora will go undisturbed aiding in decreased side effects. A second important difference is that microcins are less likely to be horizontally transferred due to their narrow target spectrum and complex machinery required for synthesis and export, which is often encoded on multiple genes.
A New Family of Compounds for HIV Therapy
Organization: University of Illinois, Urbana-Champaign
A Small Peptide Inhibitor of Calcium Current
Organization: University of Illinois, Urbana-Champaign
Voltage dependent calcium channels contribute to the inward movement of calcium ions into cells. Calcium is an important regulator of a variety of cellular processes. The calcium currents generated by the activity of calcium channels are necessary for the electrical activity and activation of cardiac and smooth muscle and are involved in the generation of electrical activity of nerves and in synaptic transmission. Calcium currents are also important in the regulation of cell growth and differentiation and in the regulation of the release of ...
Universal Procoagulant for Performing aPTT ad PT Clotting Tests
Organization: University of Illinois, Urbana-Champaign
Polyphosphate as a Hemostatic Agent
Organization: University of Illinois, Urbana-Champaign
A New Cancer Therapy Using Folate/Anti-T-Cell Antibody Conjugates
Organization: University of Illinois, Urbana-Champaign
Selective Apoptotic Induction in Cancer Cells
Organization: University of Illinois, Urbana-Champaign
Numerous in vitro studies have been completed for PAC-1 to demonstrate its mechanism of action, efficacy, and activity across a wide range of cancer types. Human tumor xenografts models have confirmed the correlation between activity of PAC-1 and reduction in tumor volume. In cancer cells, parts of the apoptotic cascade are often mutated, resulting in a cellular system that is incapable of apoptotic death when exposed to the standard chemotherapeutic agents. The small molecule, PAC-1, directly activates procaspase-3 to active caspase-3 ...
Therapeutic Scheme for Human Basigin
Organization: University of Illinois, Urbana-Champaign
Organization: University of Illinois, Urbana-Champaign
Peptide-Binding Scaffold for Protein Chip Development
Organization: University of Illinois, Urbana-Champaign
Organization: University of Illinois, Urbana-Champaign
Combatting Biofilms by Disrupting Bacteria Quorum Sensing
Organization: Wisconsin Alumni Research Foundation (WARF)
Bacteria can grow into harmful communities called biofilms that are present almost everywhere on earth – from hospitals to food facilities. Biofilms are especially difficult to clear because they are encased in a protective extracellular matrix that resists host immune response and standard antibiotics. For many bacteria species, biofilm formation is under the direct control of the cell-cell signaling pathway termed quorum sensing (QS). QS systems coordinate important life-cycle processes like swarming and conjugation. Disrupting QS in ...
Organization: PARTEQ Innovations, Queen's University
Cytochroma Inc. is a clinical stage specialty pharmaceutical company that designs, develops and commercializes prescription products to treat and prevent the clinical consequences of vitamin D insufficiency and secondary hyperparathyroidism (SHPT) associated with chronic kidney disease (CKD). The Company has an advanced portfolio of new therapies designed to safely and effectively treat patients with vitamin D insufficiency and SHPT associated with Stage 3, 4 or 5 CKD. In addition, Cytochroma is developing novel therapies to treat elevated ...
Organization: PARTEQ Innovations, Queen's University
Nometics, Inc. is focused on cancer treatment. Using clinically established and approved nitric oxide (NO) donors, the Company's founding researchers demonstrated in both pre-clinical and clinical trials that tumour growth can be slowed in numerous types of cancer including prostate, non-small cell lung and colorectal. Through the establishment of a new class of therapy, Nometics Inc. expects to redefine the paradigm of cancer treatment.
Organization: PARTEQ Innovations, Queen's University
DUSA Pharmaceuticals, Inc.? (NASDAQGM: DUSA) is a fully integrated specialty pharmaceutical company focused primarily on the development and marketing of its Levulan? photodynamic therapy (PDT) technology platform used in conjunction with it?s proprietary light source, the BLU-U? Blue Light Photodynamic Therapy Illuminator.
Organization: Wisconsin Alumni Research Foundation (WARF)
ioGenetics is engaged in the design and development of novel recombinant proteins, with particular emphasis on fusion protein anti-microbials and anti-infectives. Its lead products are anti-cryptosporidial drugs.
Organization: Wisconsin Alumni Research Foundation (WARF)
Bridge to Life Ltd. plans to generate revenue by selling Belzer UW? brands of cold storage and kidney perfusion solutions and use those revenues to help pay for animal and clinical studies to develop a very promising patented new technology?fusogenic liposomal ATP, which transports high volumes of ATP into cells. ATP is essential for cell and organ health. Early animal studies show that fusogenic liposomal ATP may improve the condition of organs to be transplanted that would be a substantial advance in organ transplantation. Other potential ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Centrose is in business to discover novel drug leads using CarboConnect?, a proprietary discovery platform that rapidly enhances drugs and drug leads through the chemical and/or enzymatic attachment of "unusual sugars." Through CarboConnect, Centrose develops improved, proprietary versions of existing drugs and drug leads with large market potential and where significant unmet medical needs exist. Up until now, no one had exploited the potential of "unusual sugars" in drug discovery. The company's first sugar enhanced lead has shown strong ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Colby is a clinical stage cancer therapeutic drug company developing small molecule drugs that modulate key metabolic oxidative stress (OS) pathways in prostate inflammation & cancer (PCa). These drugs are being developed with access to grants from the National Institutes of Health, Department of Defense, the Prostate Cancer Foundation and funds from private investors. Colby has in-licensed these drugs from WARF. Colby operates in Sunnyvale and Menlo Park, Calif., and has collaborations in Wisconsin.
Organization: Wisconsin Alumni Research Foundation (WARF)
ConjuGon? Inc. is developing novel technologies for the prevention and treatment of bacterial infections. The rise of antibiotic-resistant, pathogenic bacteria is quickly becoming a crisis and many times, these infections are acquired when patients are treated in hospitals and other healthcare facilities for unrelated conditions. ConjuGon's? first product to prevent Catheter-Associated Urinary Tract Infections will soon enter Phase 1 human clinical trials and a second product for wound infections is in preclinical testing. ConjuGon? is based ...
Organization: Wisconsin Alumni Research Foundation (WARF)
Deltanoid Pharmaceuticals Inc. was founded in 1999 by Drs. Hector DeLuca and Margaret Clagett-Dame, two leading research scientists in biochemistry at UW-Madison, to ensure that promising technologies that have the potential to improve human health are developed for commercialization. Deltanoid Pharmaceuticals is a drug development company involved in breakthrough treatments for osteoporosis, renal disease, psoriasis and other disease targets. The company specializes in designing advanced vitamin D analogs, and several of its vitamin D-based ...
Organization: Wisconsin Alumni Research Foundation (WARF)
FluGen Inc. was established in 2007 to develop faster and more effective ways to prevent and treat pandemic and seasonal influenza. The company leverages technologies from the laboratories of Dr. Yoshihiro Kawaoka, one of the world's foremost authorities on influenza. FluGen is located in the University Research Park and has access to high level BSL-3 and GMP manufacturing facilities. FluGen's business is focused on high yield vaccine manufacturing, pandemic and seasonal vaccine candidates and therapeutics for treating influenza.
Organization: Wisconsin Alumni Research Foundation (WARF)
Longevity Biotech Inc. is a preclinical biotechnology company focused on developing novel therapeutics by utilizing a proprietary 'protein-like' molecular scaffold. Through the specific incorporation of non-natural amino acids, the Hybridtide? scaffold affords several key advantages, specifically structural and digestive stability, while retaining biologic activity. These advantages uniquely allow Longevity to pursue the so-called 'undruggable' drug targets. Initial development efforts are focused primarily on capital-efficient orphan ...
Organization: Wisconsin Alumni Research Foundation (WARF)
NeuroGenomeX (NGX) Inc. is an early stage company developing a drug, 2-deoxy-D-glucose (2DG), for patients with intractable epilepsy. Three million people in the U.S. have epilepsy. Half of these people still experience seizures even with taking current medications. Because 2DG has a different mechanism of action compared to currently marketed epilepsy drugs, NGX believes 2DG may significantly reduce seizure frequency in intractable epilepsy patients. 2DG has positive results in four different animal models of epilepsy that are very ...
Organization: Wisconsin Alumni Research Foundation (WARF)
ProCertus BioPharm is an oncology-based pharmaceutical company whose primary mission is to protect cancer patients against the side effects of chemotherapy and radiotherapy.
Organization: Wisconsin Alumni Research Foundation (WARF)
Quintessence Biosciences is a private, preclinical stage biopharmaceutical company developing novel, proprietary, anti-cancer compounds based on its EVade? ribonuclease technology platform. In vitro and in vivo preclinical data to date has demonstrated an excellent efficacy profile in murine xenograft models relative to marketed anti-cancer drugs. Additional anti-cancer drug candidates using targeting mechanisms and other mechanisms to enhance the pharmacokinetic profile of EVade? Ribonucleases are under development.
Synthetic Vitamin D Protects Bone Strength in Kidney Failure Patients
Organization: Wisconsin Alumni Research Foundation (WARF)
A serious side effect from kidney failure is the depletion of vitamin D hormone, which is manufactured by the kidneys and regulates calcium absorption from the intestines. Without adequate levels of vitamin D hormone in the bloodstream, the body cannot process enough calcium from digested food and instead must draw calcium into the blood from the skeleton. Over time this leads to weakened, brittle bones that break easily. To fight this condition, in the early 1990s, scientists at the University of Wisconsin-Madison invented paricalcitol, a ...
