Gene Therapy Approach for Cardiac Regeneration

Background

Cyclin A2 is the key genetic switch that mediates cardiac muscle regeneration and repair. It is the only cyclin regulating the two major checkpoints of the cell cycle, the G2/M transition and the G1/S transition. However, in mammals, cyclin A2 is silenced in hearts at birth. Mount Sinai’s researchers have demonstrated that using a gene therapy approach, cyclin A2 can be temporarily activated to induce cytokinesis in cardiomyocytes and replace heart muscle cells lost during a heart attack. The human gene therapy vector is designed to prevent oncogenicity or other adverse off-target effects.

Technology Overview

Mount Sinai’s researchers have demonstrated that using a gene therapy approach, cyclin A2 can be temporarily activated to induce cytokinesis in cardiomyocytes and replace heart muscle cells lost during a heart attack. The human gene therapy vector is designed to prevent oncogenicity or other adverse off-target effects.

No other approach has exhibited such properties in a large animal that mimics human hearts. With respect to ES-derived and iPS-derived cardiomyocytes, ES approach required 1 billion cardiomyocytes per primate heart and iPS cells induced ventricular arrhythmias.

Stage of Development

• Enhances cardiac function in infarcted porcine hearts
• Induce cardiac repair in small-animal models of myocardial infarction
• Complete cytokinesis in adult porcine and human cardiomyocytes
• Improves post-MI ejection fraction (EF) and averts the progression to heart failure

Benefits

• The only technology known to induce human cardiomyocytes cytokinesis
• Proof of concept has been established in several animal models

Applications

• In vivo regeneration of cardiomyocytes and replaces lost heart muscles cells to treat range of cardiac disorders (i.e. myocardial infarction, chronic heart failure, heart attack)
• Gene therapy vector has shown to be safe and currently in phase 3 trial