Melissa Spencer, professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, was awarded an MDA research grant totaling $390,000 over three years to study the role of an enzyme called calpain 3 in type 2A limb-girdle muscular dystrophy (LGMD2A).
With colleagues, Spencer has demonstrated that characteristics and disease processes of LGMD2A are different from those seen in other dystrophies.
In Duchenne muscular dystrophy and other types of LGMD, the muscle cell membrane is weakened from the genetic mutation and the muscle cells die, Spencer explains. "In LGMD2A, muscle membranes remain intact, a finding which has left researchers without an explanation for the underlying mechanism of disease."
LGMD2A is caused by mutations in the CAPN3 gene, which carries genetic instructions for building a protein called calpain 3. Over the last decade, Spencer's team has generated numerous research mouse models that have provided insight about the biological function of calpain 3 in muscle development and muscle growth, but it's remained unclear how CAPN3 mutations lead to muscle dysfunction.
The team discovered that muscles lacking calpain 3 have severe deficits in the signaling pathways responsible for muscle growth — particularly the calcium calmodulin kinases (CaMK) pathway.
Now Spencer is working on determining the relationship between calpain 3 and CaMK signaling.
Spencer's work could uncover the underlying defects for LGMD2A and lead to therapeutic targets for stimulating muscle growth in the setting of muscle degeneration. It also could shed light on other related muscular dystrophies, such as multiminicore disease.
Funding for this MDA grant began Aug. 1, 2012.