{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:28:34Z","timestamp":1792985314851,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014926","name":"Acceleron","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014926","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE\u2010083 could safely increase muscle volume and improve functional outcomes in adults with FSHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants were at least 18\u2009years old and had FSHD1\/FSHD2. Part 1 was open label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double\u2010blind for 6\u2009months, evaluating ACE\u2010083240\u2009mg\/muscle vs placebo injected bilaterally every 3\u2009weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6\u2009months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6\u2010minute walk test, 10\u2010meter walk\/run, and 4\u2010stair climb (TA group), and performance of upper limb midlevel\/elbow score (BB group). Strength, patient\u2010reported outcomes (PROs), and safety were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least\u2010squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%\u201023.0%) in the BB group (<jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.0001) and 9.5% (3.2%\u201015.9%) in the TA group (<jats:italic>P<\/jats:italic>\u00a0=\u2009.01). CMV increased significantly in the BB and TA groups and FF decreased in the TA group. There were no consistent improvements in functional or PRO measures in either group. The most common adverse events were mild or moderate injection\u2010site reactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Significant increases in TMV with ACE\u2010083 vs placebo did not result in consistent functional or PRO improvements with up to 12\u2009months of treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27558","type":"journal-article","created":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T05:44:42Z","timestamp":1650087882000},"page":"50-62","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Randomized phase 2 study of<scp>ACE<\/scp>\u2010083, a<scp>muscle\u2010promoting<\/scp>agent, in facioscapulohumeral muscular dystrophy"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-5315","authenticated-orcid":false,"given":"Jeffrey M.","family":"Statland","sequence":"first","affiliation":[{"name":"Department of Neurology 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabi N.","family":"Tawil","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Elman","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanette C.","family":"Joyce","sequence":"additional","affiliation":[{"name":"University of California Davis Medical Center Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn R.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine Kennedy Krieger Institute Baltimore Maryland 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B.","family":"Shieh","sequence":"additional","affiliation":[{"name":"University of California Los Angeles Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wicklund","sequence":"additional","affiliation":[{"name":"University of Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-7486","authenticated-orcid":false,"given":"Josep","family":"Gamez","sequence":"additional","affiliation":[{"name":"Department of Medicine, GMA Clinic European Reference Network on Rare Neuromuscular Diseases (ERN EURO\u2010NMD) and Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Bodkin","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine Indianapolis Indiana 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