Leslie Leinwand, professor of molecular, cellular and developmental biology at the University of Colorado in Boulder, was awarded an MDA research grant totaling $338,775 over a period of three years to study the causes and treatment of Laing distal myopathy (MPD1).

MPD1 is an inherited muscle disease characterized by early and selective weakness of the lower leg that affects ankle and great toe bending. With time, the disease progresses to other muscles, including those of the neck and face. MPD1 is caused by mutations in a gene called MYH7, which encodes a protein called myosin heavy chain-ß. This protein works in heart and skeletal muscle to create the pulling force that allows muscles to contract, Leinwand says, “but how these mutations lead to disease is unknown.”

Her goal is to learn more about how mutations in MYH7 cause the cellular defects that are at the root of MPD1. Specifically, she is interested in determining the effects of mutations on the ability of multiple myosin proteins to link together, which they must do to function properly. She thinks it’s likely that a defect in that linking ability may reduce the stability of sarcomeres, the basic unit of muscle that exerts the pulling force.

She also will create a mouse model of MPD1 in order to better study the effects of mutation and to test potential therapies. “We hope that our experiments will expose the pathogenesis of the disease and will lead to a successful molecular treatment for MPD1, for which there is currently no treatment,” says Leinwand.

Funding for this MDA grant began Feb. 1, 2013.