Three slides at regular intervals were stained per hindlimb specimen. The authors declare that no conflict of interest exists. Although the antiinflammatory and antifibrotic effects of rapamycin make this an enticing option to treat patients with muscle injury, studies have shown that mTOR inhibition actually has a detrimental effect on muscle size after injury 230
Figure 4 Rapamycin after injury reveals improved myofiber size with hyperactive BMP signaling. Therefore, we examined whether rapamycin similarly reduces or eliminates fibrosis in this model.
Mice assigned to treatment groups received Ad. Cell size is determined by the balance between protein synthesis and degradation. These wild-type reporter mice did not receive rapamycin because they did not show evidence of long-standing fibrosis.
These findings underscore an approach in which 2 therapeutics rapamycin and BMP ligand can offset each other, leading to an improved outcome. To study the effect of BMP signaling on myofiber injury, we used a mutant reporter mouse with the floxed caAcvr1 transgene.
An additional limitation is that we were unable to assess functional metrics in these mice. Therefore, in addition to preventing ectopic bone formation 29 , rapamycin may be able to alleviate additional muscle pathology in these patients. Go to The Journal of Clinical Investigation.