Principal Investigator: Osha Roopnarine, Ph.D.
Duchenne Muscular Dystrophy (DMD) is an inherited disease that affects young boys by the age of 12 years, and progresses to eventual death in their late teens or young adulthood.. It is caused by a deficiency of the dystrophin protein in muscle cells. Current gene therapy research of degenerating skeletal muscle in DMD focuses on skeletal muscle replacement or dystrophin and or utrophin gene replacement. However, studies have shown that gene rescue of dystrophin in the skeletal muscle does not reverse DMD cardiomyopathy. This suggests that another cardiac muscle protein, such as myosin, may be a determinant for cardiomyopathy in affected DMD patients. This is very plausible since dystrophic skeletal muscle contains a higher amount of the slower isoform of myosin, and both skeletal and cardiac muscle fiber force is decreased significantly in dystrophic muscle. The nature of myosin changes is unknown in the DMD heart. Therefore, determining the molecular role of cardiac myosin is necessary before full therapeutic measures for DMD cardiomyopathy can be developed. Myosin and actin are the two main contractile proteins in muscle and are arranged as filaments in the muscle. Myosin is the molecular motor of muscle and provides the energy for muscle contraction by hydrolyzing ATP. We plan to determine the role of myosin in DMD cardiomyopathy by assessing whether cardiac myosin switching occurs and whether the changes in contractility of dystrophic cardiac muscle fibers can be explained by structural differences in cardiac myosins. This study will give us important insight and clarification about the mechanism of DMD cardiomyopathy.