DR. ISABELLE RICHARD, GENETHON

Genetic defects in calpain 3 lead to Limb-Girdle Muscular Dystrophy type 2A, a disease of the skeletal muscle that affects predominantly the proximal limb muscles. There is no treatment for this disease to date. In an attempt to define a therapeutic strategy for LGMD2A, Dr. Richard's lab tested viral-mediated gene transfer of the CAPN3 cDNA in an animal model deficient in calpain 3. Efficient and stable transgene expression was obtained in the skeletal muscle after intramuscular and loco-regional administration. Moreover, its presence resulted in improvement of the histological features and in therapeutic efficacy at functional level. However, a cardiac toxicity that they related to an unregulated activity of calpain 3 was subsequently observed when the vectors were transferred using systemic administration. Following these results, Dr. Richard’s lab designed second generation vectors for skeletal muscle restricted expression. They showed that they were able to suppress the cardiac toxicity. Now, the research team needs to ascertain that the level of calpain 3 expressed in the skeletal muscles with the new vectors is sufficient to correct the pathology and that there is no toxicity of the transgene in other organs.

C3 organized and hosted the first U.S. scientific conference focused solely on LGMD2A: "Clinical Characteristics and Pathogenic Mechanisms of LGMD2A/calpainopathy". On October 27, 2011, twenty-four esteemed scientists from eight countries attended the workshop. A book containing abstracts submitted by the presenters is available here. The second global conference organized by C3 is slated for November 2013.

C3 sponsored "2012 New Directions in Biology and Disease of Skeletal Muscle Conference", which highlighted current developments in muscle biology, disease, and therapy with presentations by leading international researchers. More information is available here.

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C3KO mouse expression analysis: downregulation of the muscular dystrophy Ky protein and alterations in muscle aging, click here

Calpain 3, the Gatekeeper of Proper Assembly, Turnover and Maintenance, click here

Molecular and Cellular Basis of Calpainopathy, click here

Slug is a Novel Downstream Target of MyoD, click here

For a review of calpainopathy sponsored by GeneReviews
click here

For a review of calpainopathy sponsored the National Center for Biotechnology Information,
click here