2017 Therapeutic/Indication Pairing Projects

In summer and fall 2017, NCATS issued 10 Therapeutic/Indication Pairing projects. 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:

Computational Repurposing of Chemotherapies for Pulmonary Hypertension

University of Pittsburgh at Pittsburgh

Principal Investigator: Stephen Y. Chan, M.D., Ph.D., FAHA
Grant Number: 1-UH2-TR-002073-01

Project investigators will test a new mathematical algorithm to determine if specific combinations of chemotherapies ― drugs that have been tested for treatment of cancer ― are effective in treating pulmonary hypertension (PH). There are few effective medications for PH, a disease that affects the blood vessels in the lungs. If successful, this work could accelerate tests for two chemotherapies for individuals with PH and accelerate the development of new molecular inhibitors.

Learn more about this project in the NIH RePORTER.

Preclinical Evaluation of Vorinostat in Alopecia Areata

Columbia University Health Sciences

Principal Investigator: Angela M. Christiano, Ph.D.
Grant Number: 1-UH2-TR-002090-01

Alopecia areata (AA) is a common autoimmune form of hair loss that affects approximately six million people in the United States. The project team has performed genetic and gene expression studies in AA and identified a drug candidate to repurpose. They will evaluate the drug for preclinical efficacy in AA.

Learn more about this project in the NIH RePORTER.

Preclinical Testing of a Novel Therapeutic for Nonalcoholic Steatohepatitis

Icahn School of Medicine at Mount Sinai

Principal Investigator: Joel Thomas Dudley, Ph.D.
Grant Number: 1-UH2-TR-002077-01

Nonalcoholic steatohepatitis, or NASH, is a serious and growing health threat in the United States, affecting nearly 5 percent of the population. The goal of this project is to see if a drug with established safety information can be repurposed as a potential new treatment for NASH. If successful, the work could accelerate efforts to bring new therapies to the clinic for treatment of NASH.

Learn more about this project in the NIH RePORTER.

Repurposing Pyronaridine as a Treatment for Chagas Disease

Collaboration Pharmaceuticals, Inc.

Principal Investigators: Sean Ekins, Ph.D., D.Sc., Collaboration Pharmaceuticals, Inc.; Jair Lage de Siqueira Neto, Ph.D., University of California, San Diego; and Ester Cerdeira Sabino, M.D., Ph.D., University of Sao Paulo
Grant Number: 1-UH2-TR-002084-01

Approximately 6 to 7 million people in Latin America are infected with the eukaryotic parasite Trypanosoma cruzi, the cause of the deadly Chagas disease. Investigators on this project identified an antimalarial drug using computational Bayesian repurposing methods. The project team will test for the minimum effective dose to treat the acute model of this disease, while assessing the potential for combination therapy.

Learn more about this project in the NIH RePORTER.

Single-Cell-Driven Drug Repositioning Approaches to Target Inflammation in Atherosclerosis

Icahn School of Medicine at Mount Sinai

Principal Investigator: Chiara Giannarelli, M.D., Ph.D.
Grant Number: 1-UH2-TR-002067-01

Atherosclerotic cardiovascular disease (CVD) is the leading cause of mortality and disability worldwide. Even in patients treated with the best standard-of-care programs, residual illness and death remain high. New strategies that directly target atherosclerosis—the main cause of CVD—are needed. This project may provide proof-of-concept evidence for the use of network-driven computational approaches to identify new therapies for atherosclerosis. Using quantitative non-invasive imaging as a translational platform for measuring drug efficacy in a preclinical setting could facilitate a smooth and fast translation of new therapeutics into clinical trials.

Learn more about this project in the NIH RePORTER.

Impact of SAR152954 on Prenatal Alcohol Exposure-Induced Neurobehavioral Deficits

University of New Mexico Health Sciences Center

Principal Investigator: Daniel D. Savage, Ph.D.
Grant Number: 1-UH2-TR-002082-01

At least 2 to 4 percent of children born in the United States each year are at risk for having prenatal alcohol-associated brain damage, which can cause cognitive disabilities. This research project team will examine the effectiveness of a novel class of drugs for improving neurophysiologic and learning deficits in a well-established animal model of Fetal Alcohol Spectrum Disorder.

Learn more about this project in the NIH RePORTER.

An Endoplasmic Reticulum Calcium Stabilizer for the Treatment of Wolfram Syndrome

Washington University in St. Louis

Principal Investigator: Fumihiko Urano, M.D., Ph.D.
Grant Number: 1-UH2-TR-002065-01

Endoplasmic reticulum (ER) is an emerging target for human chronic diseases, especially in diabetes and neurodegeneration. Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by juvenile-onset diabetes and neurodegeneration; it is considered a prototype of ER disorder. This project may lead to a breakthrough for treatments of such common diseases as diabetes, neurodegeneration and blindness.

Learn more about this project in the NIH RePORTER.

Utilization of Phenotypic Precision Medicine to Identify Optimal Drug Combinations for the Treatment of Hepatocellular Carcinoma

University of Florida

Principal Investigators: Ali Zarrinpar, M.D., Ph.D., University of Florida; and Dean Ho, M.S., Ph.D., University of California, Los Angeles
Grant Number: 1-UH2-TR-002087-01

This project applies a computational platform (Phenotypic Precision Medicine) to optimize combination therapy for the treatment of liver cancer. Project researchers will demonstrate the ability to devise novel combination therapies and then plan a clinical trial to test the feasibility and efficacy of this approach to treat liver cancer.

Learn more about this project in the NIH RePORTER.

Targeting Glucose Metabolism for the Treatment of Hepatocellular Carcinoma

University of California, San Francisco

Principal Investigator: Bin Chen, Ph.D.
Grant Number: 1-R21-TR-001743-01

Hepatocellular carcinoma is the third leading cause of cancer-related death globally, and effective treatments are limited. This project will use the recent public molecular datasets to predict drugs for hepatocellular carcinoma and evaluate them using thorough preclinical models.

Learn more about this project in the NIH RePORTER.

Application of a Repurposed FDA Approved Drug as a Local Osteogenic Agent

Emory University

Principal Investigators: Nick J. Willett, Ph.D., and Sreedhara Sangadala, Ph.D.
Grant Number: 1-R21-TR-001751-01

This project will investigate the potential of a family of Food and Drug Administration-approved small molecules to be repurposed as a therapeutic strategy to induce bone formation for spine fusion.

Learn more about this project in the NIH RePORTER.