A Phase 2B Multicenter Study of the Comparative Efficacy and Safety of Transendocardial Injection of MSC in Patients with Nonischemic Dilated Cardiomyopathy

This proposal addresses the FY19 PRMRP Topic Area of Cardiomyopathy. Non-ischemic dilated cardiomyopathy (NIDCM) is one of the more common causes of heart failure in young adults, a leading cause of disability and death, and accounts for approximately 50 percent of heart transplants performed. As such this disorder is a lead candidate for cell-based therapy. Patients with NIDCM have an enlarged, structurally damaged heart muscle with reduced function. Our group and others have shown that cell-based therapy using mesenchymal stem cells (MSCs) holds great promise as a new approach to produce durable and sustainable improvements in heart function and structure in patients with heart failure due to NIDCM. If these effects can be clinically established and optimized, there is enormous potential for improving clinical outcomes for the many patients suffering from NIDCM. Our group has extensive experience with catheter delivery of bone marrow-derived MSCs in patients with heart failure due to heart attack as well as NIDCM. There is substantial scientific and public interest for cardiac regenerative cell therapy strategies, based on pre-clinical, translational, and early Phase I/II clinical studies. In the POSEIDON-DCM clinical trial, we identified a meaningful increase in cardiac function in a cohort of patients with NIDCM who received MSCs. One-third of the patients transitioned from heart failure with reduced cardiac function to heart failure with recovered function, which is associated with reductions in disease-related symptoms and complications as well as death. Since NIDCM is associated with genetic mutations in a significant proportion of patients, we hypothesized that NIDCM genotype influences patient responsiveness to MSC therapy. Accordingly, we conducted a sub study in the POSEIDON-DCM patients by performing a detailed genotyping using a comprehensive cardiomyopathy gene panel.