IND-enablingEpicardial Biopharmaceutical in the Diabetic Heart

ABSTRACT Diabetes mellitus (DM) is caused by inadequate insulin secretion or an inability to respond appropriately to secreted insulin, which leads to chronic elevated blood sugar levels (hyperglycemia). An estimated 171 million people worldwide have DM, and the prevalence of DM will more than double over the next 2 decades. Diabetic patients have increased rates, severity, and complexity of atherosclerotic Coronary Artery Disease and increased likelihood of undergoing surgical revascularization procedures. None of the current coronary revascularization procedures regenerate the myocardium. This project will test the efficacy of a bioabsorbable rhFSTL1*-containing collagen matrix (EpicaPatch), applied to the epicardium overlying the damaged myocardium in infarcted diabetic pigs. Phase 1 is designed to obtain proof of feasibility and, if successful, Phase 2 describes IND enabling studies that would form part of a pre-IND submission to FDA to support a First in Man clinical trial. The benefits of this therapy, if successful are the addition of regenerative capacity to current revascularization procedures, therefore protecting diabetic patients from heart failure.  NARRATIVE Diabetic patients have increased rates, severity, and complexity of atherosclerotic Coronary Artery Disease (CAD) and 75% of diabetic patients die as a result of a cardiovascular cause. These patients undergo revascularization by coronary artery bypass grafts (CABG) rather than percutaneous coronary intervention. However, CABG does not regenerate the myocardium. This proposal will generate feasibility (Phase1) and proof of concept (Phase 2) for cardiac regeneration in the diabetic, infarcted animal using a bioresorbable collagen matrix containing bacterial-made human Follistatin-like 1. This matrix, when applied to the epicardial surface overlying the infarct in non-diabetic animals, regenerates the myocardium (Nature. September 2015). The goal is to add myocardial regeneration to the established revascularization benefits of CABG in the diabetic patient with ischemic heart disease. Such a demonstration, if confirmed in subsequent clinical trials, might very greatly improve the treatment of ischemic heat disease in diabetes.