Bernhard Kuhn, MD

Characterizing Molecular Mechanisms of Cardiomyocyte Proliferation Aimed at Developing New Regenerative Therapies of Cardiomyopathy
Children's Hospital Boston
Bernhard Kuhn, MD – $50,000

The inability of human hearts to replace lost heart muscle cells predisposes victims of cardiomyopathy to the development of heart failure. Currently, the only hope for the survival of these young patients is heart transplantation, but the scarcity of suitable organs and the potential of rejection seriously limit this approach. A leading hypothesis is that advanced heart failure is effectively a cardiomyocyte (heart muscle cell) deficiency disorder, in short, that cardiomyopathy leads to loss of heart cells and hence to heart failure. Therefore, novel approaches for regenerating heart muscle by inducing proliferation of cardiomyocytes could transform the therapy for heart failure. In recent studies, it was shown that mammalian cardiomyocytes, which normally stop dividing early in life, can be induced into a proliferative state by exposure to the growth factor Neuregulin 1 (NRG1) and by periostin peptide. It was proven that these treatments enhance myocardial regeneration and improve heart function in animals. The goal of this project is to understand the molecular mechanisms that underlie cardiomyocyte proliferation after birth. Microarray technology will be used to study gene expression patterns in individual cardiomyocytes during cell cycle re-entry (proliferative state) and exit (non-proliferative state). It is anticipated that study findings will generate a list of novel candidate genes that play a role in controlling the proliferation of heart muscle cells, and in helping to improve function in diseased hearts. Future directions will involve the functional characterization of the identified genes to serve as potential biomarkers for heart disease, and/or as therapeutic targets for heart muscle regeneration, thereby reducing the enormous socioeconomic burden associated with heart transplants in children with cardiomyopathy.