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Follistatin is a secreted protein that promotes muscle growth and function by sequestering these ligands extracellularly. In the present study, we evaluated the potential of ACE-083 \u2013 a locally acting, follistatin-based fusion protein \u2013 as a novel therapeutic agent for focal or asymmetric myopathies. Characterization of ACE-083 <jats:italic>in vitro<\/jats:italic> revealed its high affinity for heparin and extracellular matrix while surface plasmon resonance and cell-based assays confirmed that ACE-083 binds and potently neutralizes myostatin, activin A, activin B and growth differentiation factor 11 (GDF11). Intramuscular administration of ACE-083 caused localized, dose-dependent hypertrophy of the\u00a0injected muscle in wild-type mice and mouse models of Charcot-Marie-Tooth disease (CMT) and Duchenne muscular dystrophy, with no evidence of systemic muscle effects or endocrine perturbation. Importantly, ACE-083 also increased the force of isometric contraction <jats:italic>in situ<\/jats:italic> by the injected tibialis anterior muscle in wild-type mice and disease models and increased ankle dorsiflexion torque in CMT mice. Our results demonstrate the potential of ACE-083 as a therapeutic agent for patients with CMT, muscular dystrophy and other disorders with focal or asymmetric muscle atrophy or weakness.<\/jats:p>","DOI":"10.1038\/s41598-019-47818-w","type":"journal-article","created":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T10:22:49Z","timestamp":1565086969000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease"],"prefix":"10.1038","volume":"9","author":[{"given":"R. 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