Year 4 (NCE)
Heart disease is a leading cause of mortality. Because heart muscle has little or no regenerative capacity after birth, current therapeutic approaches are limited for the over 5 million Americans who suffer from heart failure. Our recent findings regarding direct reprogramming of a type of structural cell of the heart, called fibroblasts, into cardiac muscle-like cells using just three genes offers a novel approach to achieving cardiac regeneration. In the last reporting period we have tested this approach in large animals (pigs) and seen an improvement in cardiac function after cardiac injury with the therapeutic approach. We also developed a chemical means for enhancing the efficiency and speed of reprogramming cells and shown that this results in 5-fold more new heart muscle in mice. Finally, we have developed a new viral vector with which to deliver the therapeutic project in human and pigs and shown that this vector can convert human cells efficiently. We are now close to finalizing a therapeutic product that could be packaged in the viral vector.