Understanding genetic errors that affect myosin in cardiomyopathy

β-cardiac myosin mutations: triggers for the development of hypertrophic and dilated cardiomyopathies

Individuals with inherited genetic errors in heart muscle proteins are at risk of sudden death at any age. This is because the error leads to two major types of heart disease: a thickened heart wall (called hypertrophic cardiomyopathy); or a weakened heart wall (called dilated cardiomyopathy). Both diseases mean that the heart can no longer function effectively. Researchers know that at least 300 of these errors (called genetic mutations) affect one vital heart protein called myosin, which helps the heart muscle contract and relax in a coordinated way. However, studies have not been able to fully identify how these errors lead to disease. Professor Michael Geeves from the University of Kent will investigate the effects on an important protein in the heart called myosin, which can be abnormal due to inherited errors that lead to heart disease. Taking a different approach to previous researchers, who often study the protein in mice, Prof Geeves will study the protein purified from cells in the laboratory. He will focus on studying 10 identified errors in myosin that seem to cause a particularly severe form of heart disease through disrupting some important areas and functions of the protein. Studies in animals are not always reliable in terms of their implications for human patients, and studies that use human tissue samples are commonly obtained from those with late-stage disease when most of the damage has occurred. Professor Geeves’ approach is therefore novel and he hopes to generate more reliable results that show the changes occurring in myosin in disease in order to be able to help develop new ways to prevent or treat these diseases.