MDA awarded a research grant totaling $343,860 over a period of three years to Jeffrey Boone Miller, senior scientist at Boston Biomedical Research Institute in Watertown, Mass., and associate professor of neurology at Harvard Medical School in Boston. The funds will help support Miller’s study of the underlying causes of, and potential therapeutic strategies for, three muscular dystrophies: type 1A congenital muscular dystrophy (MDC1A/CMD), and types 2C and 2D limb-girdle muscular dystrophy (LGMD2C, LGMD2D).
During normal skeletal muscle development, immature muscle cells called myoblasts fuse together to form large, tube-shaped cells called myotubes. Myotubes ultimately mature into muscle fibers.
“We find that myotubes formed in culture from human MDC1A, LGMD2C and LGMD2D patient myoblasts, but not normal myoblasts, spontaneously undergo cell death,” Miller said.
Miller and colleagues have found that the abnormal activation of the cell death, caused by the Bax protein and its binding partner Ku70, may underlie the cell-death changes in each of the three diseases under investigation.
In his new work, Miller plans to examine the role dysregulation of the Ku70/Bax pathway plays in muscle development. He first plans to determine whether the abnormal function of proteins that modify Ku70 function cause abnormalities in muscle. In a second set of experiments, he will test the hypothesis that restoring Ku70 function to a normal level will inhibit cell death and decrease the abnormalities in human myogenic cells.
“From our results, we hope to identify potential therapeutic strategies that could be effective for multiple diseases.”
Funding for this MDA grant began February 1, 2012.