Heart failure following a myocardial infarction (MI) continues to remain a leading killer in the western world. In the United States, the estimated annual incidence of myocardial infarction (MI) is 745,000 new and 410,000 recurrent episodes. Approximately 22% of male and 46% of female MI victims become disabled with heart failure within six years of the original incident, with a total number of Americans in heart failure estimated at 5.7 million. There is a critical need to develop new therapies since end-stage heart failure is only treated through heart transplantation or left ventricular (LV) assist devices, and current pharmaceutical regimens do not adequately prevent post-MI negative LV remodeling. As an alternative to total heart transplantation, cellular cardiomyoplasty, or cell transplantation, has been explored for the treatment of myocardial infarction and heart failure;however, more recently acellular biomaterials have shown great promise in providing similar functional benefit without the complications associated with cell delivery. Existing materials have however been limited since none have been specifically for the myocardium, and none mimic the degraded post-MI extracellular matrix (ECM) they are intended to replace. The materials suffer from 1) their inability to be delivered via current catheter technology, and/or 2) their lack of complex, myocardial specific ECM cues, which promote repair. The material used for the Ventrix product is the first example of a myocardial-specific material that can be delivered via catheter to promote repair in the post-MI environment. This material is liquid at room temperature and forms a porous and fibrous scaffold upon injection into the myocardium. We have shown that it promotes cell influx, including neovascularization, preserves LV geometry and cardiac function in a rat MI model, and can be delivered through a percutaneous transendocardial approach in a porcine model. The proposed study is a key step in bringing a biomaterial product to market, which will be complementary or mostly parallel to the current heart failure pharmaceutical market. Herein, we will test the feasibility of translating this new technology by achieving the following two specific aims: 1) Evaluate the retention and distribution of VentriGelTM in a porcine myocardial infarction model after 2D versus 3D guided transendocardial percutaneous delivery and 2) Determine the influence of VentriGelTM on post-myocardial infarction negative left ventricular remodeling, cardiac function, and potential for arrhythmias in a porcine myocardial infarction model. The objective of the proposed project is to determine the optimal percutaneous delivery approach for our biomaterial product VentriGelTM, and assess its feasibility in a large animal MI model. This will provide us with adequate data to begin a large scale, powered functional study to be conducted under a Phase II SBIR. The combination of the Phase I and II studies, which will be performed according to GLP guidelines, will be submitted to the FDA as part of an IDE application. This will be the first catheter deliverable regenerative biomaterial product for treating the millions of patients suffering from MI and heart failure.
The development of alternatives to total heart transplantation for the treatment of myocardial infarction and heart failure is a necessity because of the large patient population. This proposal seeks to test the feasibility of translating a novel percutaneous biomaterial therapy for treating myocardial infarction and heart failure.
|Seif-Naraghi, Sonya B; Singelyn, Jennifer M; Salvatore, Michael A et al. (2013) Safety and efficacy of an injectable extracellular matrix hydrogel for treating myocardial infarction. Sci Transl Med 5:173ra25|