title: Wnt7a treatment ameliorates muscular dystrophy.
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.
authors.affiliation: Sprott Center for Stem Cell Research,  Ottawa Hospital Research Institute, Ottawa, ON,  Canada K1H 8L6.
authors.forename: Julia
authors.initials: J
authors.lastname: von Maltzahn
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Renaud
authors.forename: Gianni
authors.initials: G
authors.lastname: Parise
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
mesh_terms: D000818:Animals; D053672:Electrochemotherapy; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D064326:MEF2 Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*
chemical_list: D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse