{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:56:09Z","timestamp":1789703769568,"version":"4.0.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007721","name":"Cure SMA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007721","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Investigation of the safety, tolerability, and treatment effect of nusinersen treatment in non-ambulatory adults with spinal muscular atrophy (SMA).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Non-ambulatory individuals, aged 18 years or older with genetically confirmed 5q SMA were enrolled. In participants with spinal fusion, fluoroscopy guided cervical C1\u2013C2 lateral approach was used. Outcomes at 2, 6, 10, and 14 months post-treatment were compared with baseline assessment. Forced vital capacity (FVC) was the primary outcome, and RULM, HFMSE, the modified SMA-FRS, and ulnar nerve electrophysiology [compound muscle action potential (CMAP), single motor unit size, and motor unit number] were secondary. Adverse and serious adverse events and clinically significant vital sign or lab abnormalities were recorded.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Results from 12 women and 7 men (mean age: 39.7 \u00b1 13.9, range: 21\u201364 years) were analyzed. No clinically significant changes of vital signs or laboratory parameters were observed. Five participants were hospitalized for pneumonia. Other adverse events included headache, back pain, cervical injection site pain, and upper respiratory and urinary tract infections. High baseline protein\/creatinine ratio without significant change on treatment noted in 4 participants. FVC was feasible in all participants. HFMSE and RULM were not feasible in the majority of participants. FVC and functional outcomes were stable without improvement. CMAP and single motor unit potential sizes showed enlargement while motor unit numbers were stable.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Nusinersen, including C1\/C2 delivery, was safe overall and well-tolerated. Several outcome measures were limited by floor effect. Overall, treatment resulted in stability of motor outcomes, but motor unit and CMAP size were increased.<\/jats:p>","DOI":"10.3389\/fneur.2021.650532","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T19:11:39Z","timestamp":1618600299000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Safety, Tolerability, and Effect of Nusinersen in Non-ambulatory Adults With Spinal Muscular Atrophy"],"prefix":"10.3389","volume":"12","author":[{"given":"Bakri","family":"Elsheikh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Severyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songzhu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Linsenmayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tellez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Bartlett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Heintzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Sterling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Weaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Rajneesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Kolb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. David","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/gt.2017.52","article-title":"The clinical landscape for SMA in a new therapeutic era","volume":"24","author":"Talbot","year":"2017","journal-title":"Gene Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/ejhg.2011.134","article-title":"Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens","volume":"20","author":"Sugarman","year":"2012","journal-title":"Eur J Hum Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell."},{"key":"B4","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/ng0797-265","article-title":"Correlation between severity and SMN protein level in spinal muscular atrophy","volume":"16","author":"Lefebvre","year":"1997","journal-title":"Nat Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc Natl Acad Sci USA."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","article-title":"A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2","volume":"8","author":"Monani","year":"1999","journal-title":"Hum Mol Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1093\/hmg\/9.2.259","article-title":"An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN","volume":"9","author":"Lorson","year":"2000","journal-title":"Hum Mol Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1002\/ana.20473","article-title":"Natural history of denervation in SMA: relation to age, SMN2 copy number, and function","volume":"57","author":"Swoboda","year":"2005","journal-title":"Ann Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1002\/mus.21350","article-title":"An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy","volume":"40","author":"Elsheikh","year":"2009","journal-title":"Muscle Nerve."},{"key":"B10","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1097\/00125817-200201000-00004","article-title":"Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2","volume":"4","author":"Mailman","year":"2002","journal-title":"Genet Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.ncl.2020.03.002","article-title":"Spinal Muscular Atrophy in the Treatment Era","volume":"38","author":"Waldrop","year":"2020","journal-title":"Neurol Clin."},{"key":"B12","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus sham control in later-onset spinal muscular atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N Engl J Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus sham control in infantile-onset spinal muscular atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N Engl J Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e2492","DOI":"10.1212\/WNL.0000000000007527","article-title":"De vivo, nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1\/2 studies","volume":"92","author":"Darras","year":"2019","journal-title":"Neurology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"453","DOI":"10.3233\/JND-190416","article-title":"Safety and treatment effects of nusinersen in longstanding adult 5q-SMA type 3 - a prospective observational study","volume":"6","author":"Walter","year":"2019","journal-title":"J Neuromuscul Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1007\/s00415-020-10223-9","article-title":"Nusinersen treatment significantly improves hand grip strength, hand motor function and MRC sum scores in adult patients with spinal muscular atrophy types 3 and 4","volume":"268","author":"De Wel","year":"2020","journal-title":"J. Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/S1474-4422(20)30037-5","article-title":"Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study","volume":"19","author":"Hagenacker","year":"2020","journal-title":"Lancet Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1756286420907803","DOI":"10.1177\/1756286420907803","article-title":"Experiences from treating seven adult 5q spinal muscular atrophy patients with nusinersen","volume":"13","author":"Jochmann","year":"2020","journal-title":"Ther Adv Neurol Disord."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1136\/jnnp-2020-323822","article-title":"Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3","volume":"91","author":"Maggi","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e413","DOI":"10.1212\/WNL.0000000000009914","article-title":"Nusinersen in adult patients with spinal muscular atrophy: observations from a single center","volume":"95","author":"Moshe-Lilie","year":"2020","journal-title":"Neurology."},{"key":"B21","doi-asserted-by":"publisher","first-page":"257","DOI":"10.3233\/JND-190453","article-title":"Prospective cohort study of nusinersen treatment in adults with spinal muscular atrophy","volume":"7","author":"Yeo","year":"2020","journal-title":"J Neuromuscul Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1002\/mus.26769","article-title":"Nusinersen for older patients with spinal muscular atrophy: a real-world clinical setting experience","volume":"61","author":"Veerapandiyan","year":"2020","journal-title":"Muscle Nerve."},{"key":"B23","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/mus.26756","article-title":"Outcome measures in a cohort of ambulatory adults with spinal muscular atrophy","volume":"61","author":"Elsheikh","year":"2019","journal-title":"Muscle Nerve."},{"key":"B24","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1002\/mus.25430","article-title":"Revised upper limb module for spinal muscular atrophy: Development of a new module","volume":"55","author":"Mazzone","year":"2017","journal-title":"Muscle Nerve."},{"key":"B25","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s13023-020-01367-y","article-title":"Natural history of lung function in spinal muscular atrophy","volume":"15","author":"Wijngaarde","year":"2020","journal-title":"Orphanet J Rare Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/ana.24332","article-title":"A large animal model of spinal muscular atrophy and correction of phenotype","volume":"77","author":"Duque","year":"2015","journal-title":"Ann Neurol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.nbd.2015.12.014","article-title":"The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy","volume":"87","author":"Arnold","year":"2016","journal-title":"Neurobiol Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1136\/jnnp-2020-324254","article-title":"Motor unit changes in children with symptomatic spinal muscular atrophy treated with nusinersen","volume":"92","author":"Kariyawasam","year":"2021","journal-title":"J Neurol Neurosurg Psychiatry."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.650532\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T19:11:42Z","timestamp":1618600302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.650532\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,16]]},"references-count":28,"alternative-id":["10.3389\/fneur.2021.650532"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.650532","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,16]]},"article-number":"650532"}}