{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:50:01Z","timestamp":1793346601492,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The EMBRACE study (Clinical Trials No. NCT02462759) evaluated nusinersen in infants\/children with infantile\u2010 or later\u2010onset spinal muscular atrophy (SMA) who were ineligible for the ENDEAR and CHERISH studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants were randomized to intrathecal nusinersen (12\u2010mg scaled equivalent dose; n = 14) or sham procedure (n = 7) in part 1 (~14\u2009months) and subsequently received open\u2010label nusinersen for ~24\u2009months in part 2 of the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Part 1 was stopped early after the demonstration of motor function benefit with nusinersen in ENDEAR. There were no nusinersen\u2010related adverse events (AEs) and no study discontinuations due to nusinersen\u2010related AEs. The most common AEs included pyrexia, cough, pneumonia, and upper respiratory tract infections. Motor milestone responder rates were higher in those receiving nusinersen at last available assessment (93%) than in those receiving sham procedure in part 1 (29%) or transitioned from sham to nusinersen in part 2 (83%). This functional improvement was observed despite the small sample size and shortened part 1 trial duration that undermined the power of the study to demonstrate such treatment effects at a significant level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Nusinersen demonstrated a favorable long\u2010term benefit\u2010risk profile in this broad population of individuals with infantile\u2010 or later\u2010onset SMA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27187","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T06:41:00Z","timestamp":1611729660000},"page":"668-677","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["Safety and efficacy of nusinersen in spinal muscular atrophy: The <scp>EMBRACE<\/scp> study"],"prefix":"10.1002","volume":"63","author":[{"given":"Gyula","family":"Acsadi","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology, Connecticut Children's Medical Center University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-2797","authenticated-orcid":false,"given":"Thomas O.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"M\u00fcller\u2010Felber","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, LMU Campus Innenstadt University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7145-7663","authenticated-orcid":false,"given":"Perry B.","family":"Shieh","sequence":"additional","affiliation":[{"name":"Department of Neurology UCLA Clinical and Translational Research Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randal","family":"Richardson","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Gillette Children's Specialty Healthcare  St Paul Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjana","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Neurology Seattle Children's Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Neurology and Neurotherapeutics UT Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ramirez\u2010Schrempp","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gambino","sequence":"additional","affiliation":[{"name":"Biogen  Maidenhead UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Sun","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wildon","family":"Farwell","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1996.0010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2011.09.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.04.009"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807305673"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-265"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/338627"},{"key":"e_1_2_10_8_1","unstructured":"European Medicines Agency. 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