Steven Greenway, MD
Modeling Novel Therapeutics for DCMA, a Mitochondrial Cardiomyopathy
University of Calgary, Alberta, Canada
2018 Amount Awarded – $49,184
Weak heart muscle or cardiomyopathy is common in metabolic or genetic diseases which affect cellular energy production. Given the premature death of affected children, these rare diseases represent a significant health problem. An example is dilated cardiomyopathy associated with ataxia syndrome (DCMA). DCMA is caused by mutations in DNAJC19, an essential gene whose function is poorly understood. It has been found that the mitochondria, the powerhouses of the cell, are fragmented and have abnormal function in DCMA. The Hutterites of southern Alberta, has the largest population of DCMA patients in the world and 39% of affected children die from severe heart failure despite medical therapy. It is known that the medication digoxin, improves heart function in children with DCMA through an unknown mechanism. Another potential new drug is the synthetic molecule SS-31 which protects mitochondria from damage and acts to restore their normal structure. This study will use induced pluripotent stem cells from reprogrammed patient blood cells that have been converted into cardiac muscle cells (cardiomyocytes) to identify the key problem in DCMA and evaluate the effects of digoxin and SS-31. This project has the potential to further understanding of cardiomyopathy and using a model system that could be applied to many pediatric cardiomyopathies, test drug therapies that could be used in affected children.