Protein Therapeutics Engineered to Regenerate Functional Heart Tissue

DESCRIPTION provided by applicant Myocardial infarction MI is a serious public health problem affecting million Americans each year Despite advances in treatment the one year survival rate following MI is only Furthermore the patients who survive still suffer irreversible loss of heart function due to cardiomyocyte death and subsequent scarring of the heart These patients often progress to congestive heart failure which is a growing epidemic and economic burden on the health care system Silver Creek Pharmaceuticals is developing protein therapeutics to regenerate functional heart tissue after myocardial infarction We use a combination of computational and experimental biology to design growth factor based drugs called Smart Growth Factors SGFs that can act selectively on damaged cardiomyocytes to stimulate their survival We have a proof of concept molecule that significantly preserves functional heart tissue in a rat model of MI This molecule is a fusion of a growth factor and a cellular targeting arm to a scaffold protein The explicit contributions of the targeting arm and te scaffold to the moleculeandapos s mechanism of action are unknown In Phase I of this program we aim to learn more about how the design of the molecule contributes to its function by designing building and testing SGF variants that systematically explore the effect of each molecule component on SGF function The understanding gained from these tests will enable the design of even more effective therapies which will be tested in expanded efficacy studies in Phase II PUBLIC HEALTH RELEVANCE Coronary heart disease is the single biggest killer in the United States accounting for in deaths and affecting over a million people each year After a heart attack up to one billion heart muscle cells die Silver Creek Pharmaceuticals is designing and developing a new class of drugs that work to protect these cells from death and preserve functional heart tissue