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Research

New Therapeutic Uses 2013 Project Awards

Doctor taking patient's blood pressureIn June 2013, NIH announced funding for nine cooperative agreements designed to match academic research groups with selected compounds from industry. The goal of the program is to use molecules that already have undergone significant research and development by the pharmaceutical industry to more quickly advance new treatments for patients.

The funded research projects listed below address eight disease areas and are in response to RFA-TR-12-004 and RFA-TR-12-005.


The Efficacy and Safety of a Selective Estrogen Receptor Beta Agonist (LY500307)

Academic Partner: Alan Breier, M.D., Indiana University, Indianapolis
Industry Partner: Eli Lilly and Company

Schizophrenia is a mental illness that affects about 1 percent of the population. It reduces the ability to express emotion, impairs social behavior and reduces working and verbal memory (cognitive impairment), among other symptoms. The effects can devastate relationships and reduce a person’s ability to obtain an education or hold a job, and the burden on caretakers for people with schizophrenia is high. Unfortunately, people with schizophrenia do not respond well to any medications approved by the Food and Drug Administration. The hormone estrogen appears to offer some relief from these symptoms; however, it can feminize males and cause uterine cancer and heart disease in premenopausal women. This research team will test a drug candidate that mimics estrogen’s action in the body but lacks its negative side effects to see if the drug candidate is safe and if it relieves symptoms in patients with schizophrenia. If the drug candidate proves effective, it could improve patients’ functional ability and quality of life.

Listen to Breier discuss this research:

Right-click to download a transcript (1 KB)

Learn more about this project in the NIH RePORTER.

Fyn Inhibition by AZD0530 for Alzheimer’s Disease

Academic Partners: Stephen M. Strittmatter, M.D., Ph.D., Haakon Berge Nygaard, M.D., Ph.D., and Christopher H. Van Dyck, M.D., Yale University, New Haven, Connecticut
Industry Partner: AstraZeneca

Alzheimer’s disease is a neurological disorder that worsens over time with no effective treatment to slow or halt its progression. One in eight older Americans (about 5.2 million) has Alzheimer’s, at a cost of $200 billion in 2012. As the U.S. population ages, estimates predict as many as 14 million Americans may have Alzheimer’s disease by 2050. Fyn kinase, a type of protein in the Src kinase family, is involved in triggering Alzheimer’s disease. In a mouse model, it impaired memory and reduced signals between brain cells, but removing it stopped these symptoms. This research team will test an investigational drug that blocks Fyn kinase activity, first in a mouse model, then in Alzheimer’s patients for safety. The next step will be to study the drug’s effectiveness in slowing disease progression in a larger population with mild Alzheimer’s disease. The goal is to provide evidence for a large, multisite study of the investigational drug as a therapy to slow or halt progression of Alzheimer’s disease.

Watch Strittmatter discuss this research:


Learn more about this project in the NIH RePORTER.

Medication Development of a Novel Therapeutic for Smoking Cessation

Academic Partners: Darlene H. Brunzell, Ph.D., Virginia Commonwealth University, Richmond, and Kenneth Alan Perkins, Ph.D., University of Pittsburgh
Industry Partner: Janssen Research & Development, LLC

Cigarette smoking is the leading preventable cause of death in the United States, causing nearly 1 in 5 deaths each year. Smoking causes coronary heart disease and a variety of cancers, and it increases the risk for stroke and many other conditions. The health care costs and lost productivity among cigarette smokers exceeds $200 billion annually. Despite these staggering costs, nearly 50 million Americans smoke. Most say they want to quit, but few are successful with currently approved therapies, suggesting the need for better treatment options. This research team will use studies in rodents and clinical trials in smokers to test an existing compound as a treatment for tobacco cessation. The results of this research could lead to a new drug to treat nicotine dependence and might provide an effective cessation treatment for the most vulnerable smokers.

Listen to Brunzell discuss this research:

Right-click to download a transcript (1 KB)

Learn more about this project in the NIH RePORTER.

A Novel Compound for Alcoholism Treatment: A Translational Strategy

Academic Partner: Fatemeh Akhlaghi, Pharm.D., Ph.D., University of Rhode Island, Kingston
NIH Intramural Partner: Lorenzo Leggio, M.D., Ph.D., M.Sc., National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse
Industry Partner: Pfizer

Excessive alcohol use is responsible for approximately 80,000 deaths each year in the U.S. and costs the nation about $224 billion in health care costs and lost productivity; indeed, alcohol dependence affects approximately 10 percent of the U.S. population. However, only a few drugs approved by the Food and Drug Administration are available to treat alcohol dependence, and their effects are not optimal. This research team will test an oral medication that blocks a hormone called ghrelin to see if the drug is safe and if it reduces alcohol dependence. Ghrelin stimulates appetite and also can trigger alcohol craving and consumption. Both animal and human experiments suggest that blocking ghrelin activity could be a novel and promising way to treat alcohol dependence. The research team also will seek to better understand how the ghrelin-blocking drug interacts with alcohol in humans. The investigational drug could reduce the prevalence of disease and deaths associated with excess alcohol use and may be used in further studies to treat other addictions, such as tobacco dependence.

Listen to Leggio discuss this research:

Right-click to download a transcript (1 KB)

Learn more about this project in the NIH RePORTER.

Partnering to Treat an Orphan Disease: Duchenne Muscular Dystrophy

Academic Partners: Kathryn R. Wagner, M.D., Ph.D., Kennedy Krieger Institute, Baltimore, and Stanley C. Froehner, Ph.D., University of Washington, Seattle
Industry Partner: Sanofi

Duchenne muscular dystrophy (DMD) is a severe, disabling and fatal disorder. DMD affects approximately 1 in 5,000 male births worldwide. Children are born with normal strength, lose the ability to walk in early adolescence and die in early adulthood. The only accepted treatment is corticosteroids, which offer only mild benefits and have many side effects. This research team will test an oral, investigational drug by Sanofi to see if it is effective in a mouse muscular dystrophy model and safe in young animals. This will be followed by testing for safety and ideal dose level in DMD patients. In the next phase of the study, a multisite clinical trial will test the investigational drug to provide evidence of its potential benefit to DMD patients. Because DMD is a fatal disease, this study could be a pivotal turning point in obtaining Food and Drug Administration approval for a novel DMD therapeutic.

Watch Wagner discuss this research:


Learn more about this project in the NIH RePORTER.

Reuse of ZD4054 for Patients with Symptomatic Peripheral Artery Disease

Academic Partner: Brian H. Annex, M.D., University of Virginia, Charlottesville
Industry Partner: AstraZeneca

Peripheral artery disease (PAD) is a major complication of cholesterol build-up that hardens artery walls and blocks blood flow, a condition called atherosclerosis. In PAD, this cholesterol build-up in the leg arteries, causes leg pain during walking and places major limits on a patient’s quality of life. PAD affects more than 8 million Americans, but the numbers rise with older age, diabetes and smoking, as do the associated health care costs. Cholesterol-reducing drugs, medications to relieve high blood pressure and medications like aspirin to prevent clotting are recommended for patients with PAD; however, they do not improve blood flow to the legs. This research team will test an investigational drug for its ability to improve blood flow in PAD patients’ legs. The investigational drug might relieve leg pain, help patients walk further and longer, and reduce the costs of hospitalization and treatment.

Listen to Annex discuss this research:

Right-click to download a transcript (1 KB)

Learn more about this project in the NIH RePORTER.

Therapeutic Strategy for Lymphangioleiomyomatosis

Academic Partner: N. Tony Eissa, M.D., Baylor College of Medicine, Houston
Industry Partner: AstraZeneca

Lymphangioleiomyomatosis (LAM) is a progressive lung disease in which atypical cells, originating somewhere in the body, spread throughout the lungs, gradually blocking small airways and producing cysts. Typically, the disease progresses slowly, but eventually it can restrict breathing enough to cause death. LAM almost exclusively affects women of childbearing age. At this time, no proven cure exists for LAM. This research team has discovered that a type of protein called Src kinase is active in LAM cells and is important for cell growth and cells’ ability to move around and invade tissues. This study aims to determine if blocking Src activity using an investigational drug is safe and can reduce the growth and the spread of LAM cells.

Listen to Eissa discuss this research:

Right-click to download a transcript (1 KB)

Learn more about this project in the NIH RePORTER.

Therapeutic Strategy to Slow Progression of Calcific Aortic Valve Stenosis

Academic Partners: Jordan D. Miller, Ph.D., Maurice Enriquez-Sarano, M.D., and Hartzell V. Schaff, M.D., Mayo Clinic, Rochester, Minnesota
Industry Partner: Sanofi

Calcific aortic valve stenosis is a condition in which the heart valve to the aorta narrows and cannot open fully. This disease affects 3 percent of Americans older than age 65, and more than 5 million people are diagnosed with heart valve disease of some kind each year. Even for patients with only moderate aortic valve stenosis, fewer than 40 percent survive for five years after being diagnosed. No effective treatments exist to slow progression of aortic valve calcification; replacing the heart valve is the only treatment for advanced stenosis. This research team will test the safety of a Sanofi investigational drug in heart valve disease patients. The research team will test the investigational drug to provide proof of concept in slowing progression of stenosis in humans, with the potential to reduce death and illness caused by progression of calcific aortic valve disease.

Listen to Miller discuss this research:

Right-click to download a transcript (1 KB)

Learn more about this project in the NIH RePORTER.

Translational Neuroscience Optimization of GlyT1 Inhibitor

Academic Partner: John H. Krystal, M.D., Yale University, New Haven, Connecticut
Industry Partner: Pfizer

Problems with attention, memory and planning (cognitive deficits) are core symptoms of schizophrenia, with no approved treatments. The disease affects about 1 percent of the population, and these cognitive deficits can reduce a person’s ability to obtain an education or hold a job. Schizophrenia also places a heavy burden on families and caretakers. Researchers know that abnormal function of a receptor called NMDAR, which is needed to transmit signals between brain cells, contributes to the cognitive deficits in schizophrenia. An experimental drug may reduce this abnormal function in NMDAR. Using brain imaging studies, this research team will determine the safest dose of the experimental drug in healthy subjects. A novel clinical trial will follow to assess whether the experimental drug is effective by combining it with mind exercises to treat cognitive deficits in schizophrenia patients. Restoring NMDAR function in patients’ brains might be an effective treatment for the cognitive deficits in schizophrenia.

Listen to Krystal discuss this research:

Right-click to download a transcript (1 KB)

Learn more about this project in the NIH RePORTER.

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