A cell-permeable peptide therapeutic to reduce myocardial reperfusion injury

PROJECT SUMMARY The most deadly type of heart attack, ST-segment elevation myocardial infarction (STEMI) involves blockage of the coronary artery and affects approximately 750,000 people annually in the US. While percutaneous coronary intervention (PCI) saves lives by restoring blood flow to the ischemic heart, as much as half of the long-term damage to the heart is due to the reperfusion injury, for which there is no approved therapeutic shown to significantly reduce resulting cardiac infarct size. Larger infarcts are strongly associated with reinfarction, hospitalization with heart failure, and all-cause mortality. In the proposed Phase I SBIR Small Business Transition grant, Laborecom Therapeutics Inc. is developing a novel therapeutic peptide to reduce reperfusion injury. While other therapeutics have attempted to reduce reperfusion injury by direct immune suppression or reduction in mitochondrial stress, this approach targets a motor protein uniquely expressed in endothelial cells to prevent transendothelial migration. In aim 1, the therapeutic peptide will be optimized for stability, permeability, and plasma protein binding while maintaining therapeutic activity as measured by in vitro transendothelial migration assay. In aim 2, optimized peptides will be tested head-to-head in a mouse model of myocardial infarction for their ability to impact heart function as measured by echocardiogram and limit infarct size as measured by histopathology. The successful completion of these aims will result in an optimized lead candidate for further development through a Phase II award including IND-enabling studies and testing in a swine model of myocardial infarction. In addition to scientific research, under this transition award Laborecom Therapeutics will support the career development of Dr. Lucas Shores through a tailored career development plan. This will include entrepreneurial training through local and national programs, as well as direct mentorship from serial entrepreneurs and current executives at biotechnology companies to facilitate his transition to a career as an entrepreneur and independent investigator.