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

Gene Therapy volume 14, pages 733–740 (2007)Cite this article

Abstract

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 α-sarcoglycan gene (SGCA). In the highly regenerative Sgca-null mice, survival of the α-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.

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Acknowledgements

We thank the production and the in vivo departments of Généthon, especially Muriel Durand and Nicolas Guerchet. We also thank the Howard Hughes Medical Institute (Iowa City, IA, USA) for providing us with Sgca-null mice. We thank Elisabeth Baudoin for manuscript editing. This work was funded by the Association Française contre les Myopathies, the Centre National de la Recherche Scientifique, Genopole (Evry) and the Fondation pour la Recherche Médicale.

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  1. M Bartoli and J Poupiot: These authors contributed equally to this work.

Authors and Affiliations

  1. Généthon, CNRS UMR8115, Evry, France

    M Bartoli, J Poupiot, A Vulin, F Fougerousse, L Arandel, N Daniele, C Roudaut, F Noulet, L Garcia, O Danos & I Richard

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Correspondence to I Richard.

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Bartoli, M., Poupiot, J., Vulin, A. et al. AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not α-sarcoglycan deficiency. Gene Ther 14, 733–740 (2007). https://doi.org/10.1038/sj.gt.3302928

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