Wnt7a treatment induced satellite cell expansion, myofiber hypertrophy, and a significant increase in muscle strength in mdx mice, suggesting its potential as an ameliorative treatment for DMD.
Does Wnt7a treatment improve muscle strength and hypertrophy in preclinical models of Duchenne muscular dystrophy?
Wnt7a is a promising candidate for ameliorative treatment of Duchenne muscular dystrophy based on its ability to induce muscle hypertrophy and increase strength in preclinical models.
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.
Maltzahn et al. (Mon,) conducted a other in Duchenne muscular dystrophy (DMD). Wnt7a was evaluated on Satellite cell expansion, myofiber hypertrophy, muscle strength, and contractile damage. Wnt7a treatment induced satellite cell expansion, myofiber hypertrophy, and a significant increase in muscle strength in mdx mice, suggesting its potential as an ameliorative treatment for DMD.