Daniel Bernstein, MD

iPSC-Derived Cardiomyocytes in Left Ventricular Non-Compaction Cardiomyopathy
Stanford University, Palo Alto, CA
Daniel Bernstein, MD – $50,000

Left ventricular non-compaction (LVNC) cardiomyopathy is a cause of heart failure that is increasingly being recognized in patients of all ages, but especially in children where it represents almost 10% of cases. LVNC has unique features that distinguishes it from other forms of cardiomyopathy: deep and extensive trabeculation of the left ventricle giving it a sponge-like appearance. Unlike other forms of cardiomyopathy, LVNC can present with a combination of symptoms and altered heart function, ranging from a poorly contracting heart to a heart that is stiff and resists filling, as well as life-threatening abnormal heart rhythms. LVNC has been associated with mutations in a wide variety of genes. However, the mechanisms that link a specific gene mutation to the structural and function alterations in the heart seen in LVNC are unknown. This research will use a novel technology, induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs), as a model system to study LVNC. Three families with multiple affected and non-affected members with LVNC will serve as the source for both LVNC and control iPSC-CMs. The study will (1) determine the mechanisms of structural and functional alterations in LVNC, where iPSC-CMs will be generated from LVNC and control subjects and their structure, function, growth potential and gene expression will be characterized, and (2) determine the role of altered mitochondrial function in LVNC cardiomyopathy. Mitochondria are the energy-generating source in heart muscle cells, and their function is often abnormal in patients with heart failure. The study will examine whether iPSC-CMs from LVNC subjects have alterations in mitochondrial function compared with control cells.