Myocardial infarction (MI) is a serious public health problem affecting 1.5 million Americans each year. Despite advances in treatment, the one year survival rate following MI is only 37%. 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 molecule'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 Statement:
Public Health Relevance: Coronary heart disease is the single biggest killer in the United States, accounting for 1 in 5 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.
Project Terms:
Accounting; Acute myocardial infarction; Affect; American; Animal Model; Animals; Anterior; Apoptosis; arm; Arteries; base; Binding (Molecular Function); Biological Assay; Biology; cancer cell; Cardiac; Cardiac Myocytes; Cell Death; cell injury; Cell model; Cell Survival; Cells; cellular targeting; Cessation of life; Chimeric Proteins; Cicatrix; Cloning; comparative efficacy; Congestive Heart Failure; Coronary heart disease; design; design and construction; Dose; Drug Kinetics; Economic Burden; effective therapy; Engineering; Enzyme-Linked Immunosorbent Assay; Epidemic; Family; Generations; Goals; Growth Factor; Healthcare Systems; Heart; heart function; Hour; Human; IGF1 gene; In Vitro; in vitro testing; in vivo; induced pluripotent stem cell; Infarction; Injection of therapeutic agent; Insulin-Like Growth Factor I; Ischemia; Learning; Ligation; Mammalian Cell; Modeling; Mus; Myocardial; Myocardial Infarction; Myocardium; Natural regeneration; next generation; novel therapeutics; Panthera leo; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; programs; Proteins; Proto-Oncogene Proteins c-akt; public health medicine (field); public health relevance; Rattus; Relative (related person); Reperfusion Therapy; restoration; scaffold; Scaffolding Protein; Signal Transduction; Silver; Small Business Innovation Research Grant; standard of care; Survival Rate; System; Tail; Testing; therapeutic protein; Time; Tissues; United States; Variant; Veins; Work
