AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not alpha-sarcoglycan deficiency

Gene Ther. 2007 May;14(9):733-40. doi: 10.1038/sj.gt.3302928. Epub 2007 Mar 1.


Myostatin is a negative regulator of muscle mass whose inhibition has been proposed as a therapeutic strategy for muscle-wasting conditions. Indeed, blocking myostatin action through different strategies has proved beneficial for the pathophysiology of the dystrophin-deficient mdx mouse. In this report, we tested the inhibition of myostatin by AAV-mediated expression of a mutated propeptide in animal models of two limb-girdle muscular dystrophies: LGMD2A caused by mutations in the calpain 3 (CAPN3) gene and LGMD2D caused by mutations in the alpha-sarcoglycan gene (SGCA). In the highly regenerative Sgca-null mice, survival of the alpha-sarcoglycan-deficient muscle fibers did not improve after transfer of the myostatin propeptide. In calpain 3-deficient mice, a boost in muscle mass and an increase in absolute force were obtained, suggesting that myostatin inhibition could constitute a therapeutic strategy in this predominantly atrophic disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calpain / deficiency*
  • Calpain / genetics
  • Dependovirus / genetics
  • Genetic Engineering
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Isotonic Contraction
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophies / physiopathology
  • Muscular Dystrophies / therapy*
  • Mutation
  • Myostatin
  • Sarcoglycans / deficiency*
  • Sarcoglycans / genetics
  • Transduction, Genetic / methods
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / genetics


  • Mstn protein, mouse
  • Myostatin
  • Sarcoglycans
  • Transforming Growth Factor beta
  • Calpain

Associated data

  • OMIM/253600
  • OMIM/608099