PAGE TITLE
Novel hydrogen sulfide modulators for treating or preventing heart failure
PAGE SUMMARY
Heart failure is a highly lethal disease, affecting more than 6 million adults in the United States, with a five year mortality rate of 50% in treated patients. Heart transplantation is the only currently effective treatment for heart failure and is limited by the availability of organ donors. Thus, there is an urgent need for a therapeutic that prevents the remodeling triggered by myocardial injury that leads to heart failure.
Researchers in the Drexel College of Medicine are developing a new class of drugs to treat heart failure based on modulation of the gasotransmitter hydrogen sulfide (H2S), which activates multiple protective pathways simultaneously. The therapeutic strategy targets sulfide:quinone oxidoreductase (SQOR), an enzyme that catalyzes the first irreversible step in H2S metabolism. The scientific team has identified a novel and highly selective inhibitor of SQOR. In a mouse model of heart failure (transverse aortic constriction,) treatment of with the inhibitor improves survival and mitigates pressure-induced cardiomegaly, pulmonary congestion, and dilatation of the left ventricle. The inhibitor preserves cardiac function, by impeding left ventricle hypertrophy, thus preventing the development of cardiac fibrosis.
APPLICATIONS
TITLE: Applications
Therapy for heart failure, high blood pressure, atherosclerotic plaque formation, or cardiac remodeling
Combination therapy with ACE inhibitors, beta blockers, vasodilators, nitrates, etc.
Increase physiological levels of H2S
ADVANTAGES
TITLE:Advantages
Address unmet clinical need with pharmaceutical potential solution
Improve patient survival
Decrease hospitalization rates
Mitigate myocardial remodeling that leads to heart failure
IP STATUS
Intellectual Property and Development Status
PCT patent application PCT/US20/12938
PUBLICATIONS
References
Augustyn K.D.C., Jackson M.R., and Jorns M.S. Use of tissue metabolite analysis and enzyme kinetics to discriminate between alternate pathways for hydrogen sulfide metabolism. Biochemistry, 2017, 56(7), p. 986-996.
http://pubs.acs.org/doi/10.1021/acs.biochem.6b01093
Jackson M.R., Loll P.J., and Jorns M.S. X-Ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation. Structure, 2019, 27(5), p. 794-805.
https://www.sciencedirect.com/science/article/pii/S0969212619300802?via%3Dihub
Contact Information
Dr. Robert McGrath
Senior Associate Vice Provost
Technology Management
rbm26@drexel.edu
215.895.0303