The motor protein, myosin, has fascinated BioFrontiers Chief Scientific Officer Leslie Leinwand for more than 25 years. This protein is responsible for making muscles contract in the body, but Leinwand, a professor in molecular, cellular and developmental biology, is interested in its function in one important muscle: the heart.
Myosin drives heart muscle contraction, and when this protein is mutated, it has devastating effects on the cardiovascular system. There are more than 300 known mutations in myosin, many of which cause a disease called hypertrophic cardiomyopathy. It is the most common genetic heart disease, occurring in 1 in 500 individuals, and is the leading cause of sudden death in young people.
In hypertrophic cardiomyopathy, the heart muscle becomes thickened in parts, forcing the heart to work overtime pumping blood throughout the body. Adults with this disease manage it by avoiding strenuous exercise and, in some cases, by using an implanted pacemaker. Even with those precautions, there is still the risk of sudden death.
Pediatric patients with myosin mutations can develop a more aggressive version of the disease and are left to rely on heart transplants to survive. Leinwand isn’t satisfied with treatments for this disease in children and has co-founded a biotechnology company, MyoKardia, Inc., toward developing small molecule drugs that could have promise for treating myosin protein mutations before they lead to thickening of the heart muscle.
“We can get beyond just treating the symptoms,” says Leinwand. “We have the potential to treat the root cause of this disease. If we can focus on preventing the heart muscles from thickening in the first place, we can get away from pacemakers and transplants.”