{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:45:55Z","timestamp":1790999155301,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>NURTURE (NCT02386553) is an open\u2010label study of nusinersen in children (two<jats:italic>SMN2<\/jats:italic>copies,<jats:italic>n<\/jats:italic>\u2009=\u200915; three<jats:italic>SMN2<\/jats:italic>copies,<jats:italic>n<\/jats:italic>\u2009=\u200910) who initiated treatment in the presymptomatic stage of spinal muscular atrophy (SMA). A prior analysis after ~3\u2009y showed benefits on survival, respiratory outcomes, motor milestone achievement, and a favorable safety profile. An additional 2\u2009y of follow\u2010up (data cut: February 15, 2021) are reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The primary endpoint is time to death or respiratory intervention (\u22656\u2009h\/day continuously for \u22657\u2009days or tracheostomy). Secondary outcomes include overall survival, motor function, and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Median age of children was 4.9 (3.8\u20135.5) y at last visit. No children have discontinued the study or treatment. All were alive. No additional children utilized respiratory intervention (defined per primary endpoint) since the prior data cut. Children with three<jats:italic>SMN2<\/jats:italic>copies achieved all World Health Organization (WHO) motor milestones, with all but one milestone in one child within normal developmental timeframes. All 15 children with two<jats:italic>SMN2<\/jats:italic>copies achieved sitting without support, 14\/15 walking with assistance, and 13\/15 walking alone. Mean Hammersmith Functional Motor Scale Expanded total scores showed continued improvement. Subgroups with two<jats:italic>SMN2<\/jats:italic>copies, minimum baseline compound muscle action potential amplitude \u22652\u2009mV, and no baseline areflexia had better motor and nonmotor outcomes versus all children with two<jats:italic>SMN2<\/jats:italic>copies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results demonstrate the value of early treatment, durability of treatment effect, and favorable safety profile after ~5\u2009y of nusinersen treatment. Inclusion\/exclusion criteria and baseline characteristics should be considered when interpreting presymptomatic SMA trial data.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27853","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T12:32:31Z","timestamp":1688646751000},"page":"157-170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5\u2010year update of the<scp>NURTURE<\/scp>study"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-2797","authenticated-orcid":false,"given":"Thomas O.","family":"Crawford","sequence":"first","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-6342","authenticated-orcid":false,"given":"Kathryn J.","family":"Swoboda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-0795","authenticated-orcid":false,"given":"Darryl C.","family":"De Vivo","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatrics Columbia University Irving Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4590","authenticated-orcid":false,"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disorders Post\u2010Graduate Bambino Ges\u00f9 Children's Research Hospital, IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-4879","authenticated-orcid":false,"given":"Wuh\u2010Liang","family":"Hwu","sequence":"additional","affiliation":[{"name":"Departments of Medical Genetics and Pediatrics National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9351-7054","authenticated-orcid":false,"given":"Richard S.","family":"Finkel","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurotherapeutics St. Jude Children's Research Hospital Memphis Tennessee USA"},{"name":"Division of Neurology Nemours Children's Hospital Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-7386","authenticated-orcid":false,"given":"Janbernd","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2253-5156","authenticated-orcid":false,"given":"Nancy L.","family":"Kuntz","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. 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