Project Team

Marilyn S. Jorns, PhD, Professor, Dept. of Biochemistry & Molecular Biology, Drexel University College of Medicine (DUCOM).

Howard J. Eisen, MD, Chief of Cardiology, Dept. of Medicine, DUCOM

Patrick Y. S. Lam, PhD, Senior Research Fellow, Fox Chase Chemical Diversity Center, Inc.

Michael R. Jackson, PhD, Research Assistant Professor, and Kristie Augustyn, 3rd Year

Harpreet Singh, PhD, Collaborator, Assistant Professor, Dept. of Pharmacology & Physiology, DUCOM

Boris Polyak, PhD, Collaborator, Associate Professor, Dept. of Surgery, DUCOM

Abstract

Heart failure is a highly lethal disease affecting more than 6 million adults in the United States. We propose to develop a new class of drugs to treat heart failure based on modulation of the gasotransmitter hydrogen sulfide (H2S). Heart transplantation, the only currently effective treatment for heart failure, is restricted by the availability of organ donors and immunosuppressant drugs. There is an urgent need for novel therapeutics that reduce the major risk factors and prevent the pathological remodeling triggered by myocardial injury that leads to heart failure. The attractiveness of increasing H2S levels stems from the ability of this gasotransmitter to activate multiple protective pathways at the same time. Our therapeutic strategy targets sulfide:quinone oxidoreductase (SQOR), an enzyme that sits at a key pharmacological intervention point because it catalyzes the first irreversible step in H2S metabolism. The overall objective of this Coulter proposal is to conduct proof of concept studies to demonstrate the cardioprotective efficacy of SQOR inhibitors in a mouse model of heart failure. The successful completion of this goal will derisk the technology and drive the project towards IND-directed studies and Phase I clinical trials.