A Novel Lipotherapy to Reduce Infarct Size Following Myocardial Infarction

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According to the CDC in 2013, ischemic heart disease is the leading cause of death worldwide, and in the US approximately 450,000 patients died of ischemic heart disease. It is well established in clinical practice that recanalization of the infarct related artery (IRA) using percutaneous coronary intervention (PCI) enhances myocardial salvage and outcomes in patients with ST-segment elevation myocardial infarction (STEMI). When the duration of ischemia exceeds 1 h from onset of symptoms, reperfusion injury following PCI often leads to infarct expansion due to the “no-reflow” phenomenon in the microvasculature of the “area at risk”. Multiple mechanisms are thought to contribute to “no-reflow”, and no effective treatment to ameliorate “no-reflow” and infarct expansion during reperfusion has been identified in large randomized clinical trials following STEMI and PCI. EndoProtech, Inc. has developed a novel therapeutic approach that alters the lipid content of endothelial cells (ECs) during PCI, which has a stabilizing effect on the microvascular endothelium and ameliorates “no-reflow” in the “area at risk” during reperfusion. The overall goal of this project is to demonstrate the safety and efficacy of our therapy in enhancing myocardial salvage following STEMI and PCI. The aims of this Phase II proposal are: 1. Evaluate efficacy of therapy in reducing “no-reflow” and infarct size; 2. Characterize the effect of the therapy on regenerative/reparative cells involved in early post-MI remodeling; 3. Perform pharmacokinetic studies of therapy; and 4. Determine stability of therapy under various storage conditions. Successful completion of these aims will determine: a) the effective dose of our therapy when delivered during PCI, b) the effect of the therapy on ‘no-reflow” in the area at risk, and c) protocols for optimal production and longer shelf life of the therapy. Aims are consistent with studies that will provide partial support for a new drug application to the FDA.