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Wnt7a treatment ameliorates muscular dystrophy.

Authors
  • 1
  • 1 Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6. , (Canada)
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
1091-6490
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Volume
109
Issue
50
Pages
20614–20619
Identifiers
DOI: 10.1073/pnas.1215765109
PMID: 23185011
Source
Medline
License
Unknown

Abstract

Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder of childhood marked by progressive debilitating muscle weakness and wasting, and ultimately death in the second or third decade of life. Wnt7a signaling through its receptor Fzd7 accelerates and augments regeneration by stimulating satellite stem cell expansion through the planar cell polarity pathway, as well as myofiber hypertrophy through the AKT/mammalian target of rapamycin (mTOR) anabolic pathway. We investigated the therapeutic potential of the secreted factor Wnt7a for focal treatment of dystrophic DMD muscles using the mdx mouse model, and found that Wnt7a treatment efficiently induced satellite cell expansion and myofiber hypertrophy in treated mucles in mdx mice. Importantly, Wnt7a treatment resulted in a significant increase in muscle strength, as determined by generation of specific force. Furthermore, Wnt7a reduced the level of contractile damage, likely by inducing a shift in fiber type toward slow-twitch. Finally, we found that Wnt7a similarly induced myotube hypertrophy and a shift in fiber type toward slow-twitch in human primary myotubes. Taken together, our findings suggest that Wnt7a is a promising candidate for development as an ameliorative treatment for DMD.

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