Sharlene Day, MD
Disease Pathways for MYBPC3 Mutations in Hypertrophic Cardiomyopathy
University of Michigan, Ann Arbor, MI
2015 Amount Awarded – $50,000
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart condition, and can cause sudden cardiac death and congestive heart failure. Current treatments help to treat symptoms but do not change the underlying disease process. While many of the genes that are affected in HCM patients have been identified, little is known about how they cause disease. Changes in the DNA, called mutations, can alter the structure of the protein that it encodes. Mutations in the most commonly affected gene in HCM, myosin-binding protein C, often lead to proteins that are shortened because they only being produced from one instead of two copies of the gene. It is uncertain whether a lower amount of the normal protein or the presence of the abnormal protein, is primarily responsible for causing HCM. From earlier studies, it was discovered that there is no significant reduction in the amount of normal myosin binding protein C in HCM patients with myosin binding protein C mutations. Therefore, this study will determine whether the mutant protein is causing many of the manifestations of HCM. The goal will be to eradicate these abnormal proteins from cells and alleviate the stress that they place on the surveillance systems that control the flow of proteins within cells. It is believed that the shortened mutant proteins are associating with helper proteins called chaperones to prevent them from being toxic to the cells. This study will try to enhance the activity of these chaperones to see if this facilitates their clearance. We expect that these studies will lay the groundwork for the future application of new therapies that target the underlying disease process, rather than treat symptoms and complications as they arise.