2018 Therapeutic/Indication Pairing Projects

In spring and fall 2018, NCATS issued four Therapeutic/Indication Pairing Projects awards. The funded preclinical projects are serving as “use cases” to demonstrate the utility of an independent crowdsourcing effort or a computational algorithm to predict new therapeutic uses of an existing drug or biologic. View the projects below:

Impact of SAR152954 on Prenatal Alcohol Exposure-Induced Neurobehavioral Deficits

University of New Mexico Health Sciences Center

Principal Investigators: Daniel Savage, Ph.D.
Grant Number: 5-UH2TR002082-02

At least 2% to 4% of children born in the United Staters each year are at risk for having prenatal alcohol-associated brain damage that can cause cognitive disabilities which, in turn, can lead to numerous secondary consequences including failure in school, trouble with the law, confinement, and dependent living, along with an increased risk for behavioral health problems. Currently, there are no evidence-based clinically useful pharmacotherapeutic interventions for these deficits. The long-term objective of our research program is to understand the neurobiologic bases of prenatal alcohol-induced learning deficits and, subsequently, to identify therapeutic agents whose mechanisms of action would be predicted to have clinical utility in treating the cognitive disabilities associated with Fetal Alcohol Spectrum Disorder (FASD). This research project will examine the effectiveness of a novel class of drugs for ameliorating neurophysiologic and learning deficits in a well-established animal model of FASD.

Learn more about this project in the NIH RePORTER.

Repurposing Misoprostol to Prevent Recurrence of Clostridium Difficile Infection

Vanderbilt University Medical Center, Washington University School of Medicine and University of North Carolina at Chapel Hill

Principal Investigators: David M. Aronoff, M.D. (Vanderbilt), Erik R. Dubberke, M.D. (WUSTL), and Sarah McGill, M.D. (UNC)
Grant Number: 1-U01TR002398-01 

The bacterium Clostridium difficile is a major cause of antibiotic-associated diarrhea and a leading infectious disease in U.S. hospitals. The infection can recur multiple times despite initially adequate treatment. This project builds on the results of studies that demonstrated a possible new therapeutic use for misoprostol, a drug approved by the Food and Drug Administration to treat certain types of ulcers, in preventing or treating C. difficile colitis. This team will conduct a clinical trial to test the hypothesis that patients with a primary episode of C. difficile infection who are treated with misoprostol in addition to standard therapy will have a reduced rate of C. difficile infection recurrence compared to patients receiving standard care only.

Learn more about this project in the NIH RePORTER.

Preclinical Characterization of Saracatinib for Cystic Fibrosis Therapy

Cincinnati Children’s Hospital Medical Center

Principal Investigator: Anil Jegga, D.V.M., M.Res., John Paul Clancy, M.D., Anjaparavanda P. Naren, Ph.D.
Grant Number: 1-UG3TR002612-01

The pursuit of additional therapeutics for cystic fibrosis (CF) is needed due to several limitations of currently FDA-approved therapies. Our data suggest that src kinase inhibitors have a significant therapeutic benefit in CF primarily by impacting multiple CF pathophysiological processes. Saracatinib or AZD0530, a src kinase inhibitor from AstraZeneca, is well tolerated in humans on chronic administration. We therefore propose to test this asset as a novel CF disease-modifying therapy.

Learn more about this project in the NIH RePORTER.

Repositioning AZD0530 for Surgical Treatment of Fibrodysplasia Ossificans Progressiva

Brigham and Women’s Hospital

Principal Investigator: Paul B. Yu, M.D., Ph.D.
Grant Number: 1-UG3TR002617-01

Fibrodysplasia ossificans progressiva (FOP) is a disabling genetic condition that results in the replacement of soft tissues with bone, causing profound immobility, impaired quality of life and reduced life expectancy. Attempts to remove abnormal bone in FOP to improve mobility are almost always met with the return of bone formation and often the worsening of immobility. Based on promising animal model results, this proposal tests whether an existing experimental drug, AZD0530, that has already been tested for safety in hundreds of human patients could be effective and safe in suppressing bone formation following surgical removal of bone in patients with FOP.

Learn more about this project in the NIH RePORTER.