MDA has awarded a research grant totaling $442,023 over three years to Madeleine Durbeej-Hjalt, a professor in muscle biology at Lund University (Sweden), Department of Experimental Medical Science. The grant will help support Durbeej-Hjalt's study of muscle-protein degradation processes in type 1A congenital muscular dystrophy (CMD1A).

CMD1A is caused by mutations in the gene for laminin alpha 2, a protein strand in a larger protein called merosin that connects muscle fibers to their surrounding tissue. Without the laminin alpha 2 strand, the normally three-stranded merosin protein can't perform this connective function and severe neuromuscular dysfunction results.

Although evidence indicates that loss of laminin alpha 2 leads to CMD1A, the underlying molecular mechanisms that cause muscle damage and loss in the disease remain unclear. Durbeej-Hjalt and colleagues hypothesize that muscle degeneration may be caused, at least in part, by increased destruction of muscle proteins through one or both of two major cellular protein degradation systems: the cellular "garbage can" known as the proteasome, or via the autophagic-lysosomal pathway, in which cell components are degraded and recycled through the cellular "recycle bin," or lysosome.

Durbeej-Hjalt's team has data indicating that activity in both protein degradation systems is increased when laminin alpha 2 is missing, and the investigators plan to test whether treatment with proteasome or autophagy inhibitors can block protein degradation and lead to improvement in muscle health.

Findings from Durbeej-Hjalt’s new study may generate important preclinical data that could lead to the development of therapies for people with CMD1A.

"I am extremely grateful for the MDA funding I have received since 2005," Durbeej-Hjalt said. "Without the MDA grants, my research group would not exist today."

Funding for this MDA grant began February 1, 2011.