{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:27:06Z","timestamp":1781778426220,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013780","name":"Limb Girdle Muscular Dystrophy 2i Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","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":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>In this study we report the results of a phase Ib\/IIa, open\u2010label, multiple ascending\u2010dose trial of domagrozumab, a myostatin inhibitor, in patients with fukutin\u2010related protein (FKRP)\u2010associated limb\u2010girdle muscular dystrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nineteen patients were enrolled and assigned to one of three dosing arms (5, 20, or 40\u2009mg\/kg every 4\u2009weeks). After 32\u2009weeks of treatment, participants receiving the lowest dose were switched to the highest dose (40\u2009mg\/kg) for an additional 32\u2009weeks. An extension study was also conducted. The primary endpoints were safety and tolerability. Secondary endpoints included muscle strength, timed function testing, pulmonary function, lean body mass, pharmacokinetics, and pharmacodynamics. As an exploratory outcome, muscle fat fractions were derived from whole\u2010body magnetic resonance images.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum concentrations of domagrozumab increased in a dose\u2010dependent manner and modest levels of myostatin inhibition were observed in both serum and muscle tissue. The most frequently occurring adverse events were injuries secondary to falls. There were no significant between\u2010group differences in the strength, functional, or imaging outcomes studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We conclude that, although domagrozumab was safe in patients in limb\u2010girdle muscular dystrophy type 2I\/R9, there was no clear evidence supporting its efficacy in improving muscle strength or function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27259","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T00:55:01Z","timestamp":1620521701000},"page":"172-179","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A phase Ib\/IIa, open\u2010label, multiple ascending\u2010dose trial of domagrozumab in fukutin\u2010related protein limb\u2010girdle muscular dystrophy"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2558-7798","authenticated-orcid":false,"given":"Doris G.","family":"Leung","sequence":"first","affiliation":[{"name":"Center for Genetic Muscle Disorders Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex E.","family":"Bocchieri","sequence":"additional","affiliation":[{"name":"Department of Computer Science Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Ahlawat","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"The Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwa S.","family":"Parekh","sequence":"additional","affiliation":[{"name":"Department of Computer Science Johns Hopkins University  Baltimore Maryland USA"},{"name":"The Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Braverman","sequence":"additional","affiliation":[{"name":"Department of Computer Science Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Summerton","sequence":"additional","affiliation":[{"name":"Center for Genetic Muscle Disorders Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Mansour","sequence":"additional","affiliation":[{"name":"Tulane University School of Medicine  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikia","family":"Stinson","sequence":"additional","affiliation":[{"name":"Center for Genetic Muscle Disorders Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genila","family":"Bibat","sequence":"additional","affiliation":[{"name":"Center for Genetic Muscle Disorders Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Morris","sequence":"additional","affiliation":[{"name":"Solid Biosciences  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Marraffino","sequence":"additional","affiliation":[{"name":"Pfizer, Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn R.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Center for Genetic Muscle Disorders Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neuroscience Johns Hopkins University School of Medicine  Baltimore Maryland 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