Myostatin inhibition for treatment of sarcopenia

In view of the effect that inhibition of myostatin has on skeletal muscle, researchers have been trying to find a myostatin-targeted treatment for sarcopenia since its discovery in 1997. First reported in Belgian Blue Cattle and later tested in rodents 1 McPherron AC Lee SJ Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A. 1997; 94: 12457-12461 Crossref PubMed Scopus (1566) Google Scholar , the inhibition of myostatin leads to roughly a doubling of muscle mass, leading to the description of the so-called double-muscled phenotype. In 2004, the first human case of a myostatin mutation was reported by Schuelke and colleagues 2 Schuelke M Wagner KR Stolz LE et al. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004; 350: 2682-2688 Crossref PubMed Scopus (1074) Google Scholar in a child described as extraordinarily muscular. These data suggested that inhibition of the myostatin pathway yielded similar results in several species. Together with reports that myostatin inhibition positively affects skeletal muscle mass and function in non-human animal models of muscle disease, 3 Han HQ Zhou X Mitch WE Goldberg AL Myostatin/activin pathway antagonism: molecular basis and therapeutic potential. Int J Biochem Cell Biol. 2013; 45: 2333-2347 Crossref PubMed Scopus (194) Google Scholar myostatin is a popular target for pharmaceutical development. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trialOur findings show LY treatment increases lean mass and might improve functional measures of muscle power. Although additional studies are needed to confirm these results, our data suggest LY should be tested for its potential ability to reduce the risk of falls or physical dependency in older weak fallers. Full-Text PDF