Heart failure (HF) affects 700,000 individuals yearly in the United States, accounting for $10-40 billion annual cost. Although the last ten years have seen dramatic improvements in therapeutic approaches to HF, the expanding number of patients with chronic HF and its persistently poor prognosis make it clear that additional novel treatment approaches are necessary. Recent research has identified myocyte enhancer factor 2 (MEF2) as a potentially important mediator of cardiac hypertrophy and subsequent myocardial failure. Myogen will develop high throughput screening assays and will screen for compounds that inhibit MEF2 signaling. In Phase I, Myogen demonstrated feasibility of the project by developing highly reproducible and robust HI assays for the MEF2/HDAC interaction. In Phase II Myogen will apply selected assays from Phase I for screening drug-like, small molecule compound libraries to identify inhibitors of MEF2 dependent gene activation. In Phase Ill Myogen will pursue validation experiments of identified inhibitors of MEF2 signaling, evaluating their ability to block the development of cardiac hypertrophy and heart failure in a variety of in vitro and animal models. Following validation, Myogen will pursue commercialization by advancing drug candidates into lead optimization and human clinical testing.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44HL065873-02
Application #
6549846
Study Section
Special Emphasis Panel (ZRG1-HEM-2 (10))
Program Officer
Reinlib, Leslie
Project Start
2000-09-11
Project End
2004-08-31
Budget Start
2002-09-23
Budget End
2003-08-31
Support Year
2
Fiscal Year
2002
Total Cost
$576,544
Indirect Cost
Name
Gilead Sciences, Inc.
Department
Type
DUNS #
City
Foster City
State
CA
Country
United States
Zip Code
94404