{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:42Z","timestamp":1788454842350,"version":"build-2803163510"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/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":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["CNS Drugs"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1007\/s40263-022-00899-0","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T02:02:32Z","timestamp":1643162552000},"page":"181-190","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model"],"prefix":"10.1007","volume":"36","author":[{"given":"Drew","family":"MacCannell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7987-5683","authenticated-orcid":false,"given":"Zdenek","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-7386","authenticated-orcid":false,"given":"Janbernd","family":"Kirschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-0902","authenticated-orcid":false,"given":"Michelle A.","family":"Farrar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan T.","family":"Iannaccone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2253-5156","authenticated-orcid":false,"given":"Nancy L.","family":"Kuntz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Finkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Valente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9102-5232","authenticated-orcid":false,"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"issue":"3","key":"899_CR1","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.pcl.2015.03.010","volume":"62","author":"BT Darras","year":"2015","unstructured":"Darras BT. Spinal muscular atrophies. Pediatr Clin North Am. 2015;62(3):743\u201366. https:\/\/doi.org\/10.1016\/j.pcl.2015.03.010.","journal-title":"Pediatr Clin North Am"},{"issue":"9630","key":"899_CR2","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.1016\/S0140-6736(08)60921-6","volume":"371","author":"MR Lunn","year":"2008","unstructured":"Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371(9630):2120\u201333. https:\/\/doi.org\/10.1016\/S0140-6736(08)60921-6.","journal-title":"Lancet"},{"issue":"7","key":"899_CR3","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1002\/ajmg.a.33474","volume":"152A","author":"TW Prior","year":"2010","unstructured":"Prior TW, Snyder PJ, Rink BD, Pearl DK, Pyatt RE, Mihal DC, et al. Newborn and carrier screening for spinal muscular atrophy. Am J Med Genet A. 2010;152A(7):1608\u201316. https:\/\/doi.org\/10.1002\/ajmg.a.33474.","journal-title":"Am J Med Genet A"},{"key":"899_CR4","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/1750-1172-6-71","volume":"6","author":"A D'Amico","year":"2011","unstructured":"D\u2019Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis. 2011;6:71. https:\/\/doi.org\/10.1186\/1750-1172-6-71.","journal-title":"Orphanet J Rare Dis"},{"issue":"7","key":"899_CR5","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","volume":"8","author":"UR Monani","year":"1999","unstructured":"Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AH, et al. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999;8(7):1177\u201383. https:\/\/doi.org\/10.1093\/hmg\/8.7.1177.","journal-title":"Hum Mol Genet"},{"issue":"7","key":"899_CR6","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.nmd.2015.04.009","volume":"25","author":"R Finkel","year":"2015","unstructured":"Finkel R, Bertini E, Muntoni F, Mercuri E, ENMC SMA Workshop Study Group. 209th ENMC International Workshop: outcome measures and clinical trial readiness in spinal muscular atrophy 7\u20139 November 2014, Heemskerk, The Netherlands. Neuromuscul Disord. 2015;25(7):593\u2013602. https:\/\/doi.org\/10.1016\/j.nmd.2015.04.009.","journal-title":"Neuromuscul Disord"},{"issue":"6","key":"899_CR7","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1002\/ana.25101","volume":"82","author":"SJ Kolb","year":"2017","unstructured":"Kolb SJ, Coffey CS, Yankey JW, Krosschell K, Arnold WD, Rutkove SB, NeuroNEXT Clinical Trial Network on behalf of the NN101 SMA Biomarker Investigators, et al. Natural history of infantile-onset spinal muscular atrophy. Ann Neurol. 2017;82(6):883\u201391. https:\/\/doi.org\/10.1002\/ana.25101.","journal-title":"Ann Neurol"},{"issue":"3","key":"899_CR8","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/ana.24864","volume":"81","author":"MA Farrar","year":"2017","unstructured":"Farrar MA, Park SB, Vucic S, Carey KA, Turner BJ, Gillingwater TH, et al. Emerging therapies and challenges in spinal muscular atrophy. Ann Neurol. 2017;81(3):355\u201368. https:\/\/doi.org\/10.1002\/ana.24864.","journal-title":"Ann Neurol"},{"issue":"7","key":"899_CR9","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.3390\/jcm9072222","volume":"9","author":"S Messina","year":"2020","unstructured":"Messina S, Sframeli M. New treatments in spinal muscular atrophy: positive results and new challenges. J Clin Med. 2020;9(7):2222. https:\/\/doi.org\/10.3390\/jcm9072222.","journal-title":"J Clin Med"},{"key":"899_CR10","unstructured":"Biogen. SPINRAZA (nusinersen) injection, for intrathecal use. 2020. Available from: www.spinraza.com\/content\/dam\/commercial\/specialty\/spinraza\/caregiver\/en_us\/pdf\/spinraza-prescribing-information.pdf. Accessed 25 June 2020."},{"key":"899_CR11","unstructured":"European Medicines Agency. Spinraza 12 mg solution for injection. 2017. Available from: http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/004312\/WC500229704.pdf. Accessed 25 June 2020."},{"issue":"14","key":"899_CR12","doi-asserted-by":"publisher","first-page":"6549","DOI":"10.1093\/nar\/gkw533","volume":"44","author":"MA Havens","year":"2016","unstructured":"Havens MA, Hastings ML. Splice-switching antisense oligonucleotides as therapeutic drugs. Nucleic Acids Res. 2016;44(14):6549\u201363. https:\/\/doi.org\/10.1093\/nar\/gkw533.","journal-title":"Nucleic Acids Res"},{"issue":"15","key":"899_CR13","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1101\/gad.1941310","volume":"24","author":"Y Hua","year":"2010","unstructured":"Hua Y, Sahashi K, Hung G, Rigo F, Passini MA, Bennett CF, et al. Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev. 2010;24(15):1634\u201344. https:\/\/doi.org\/10.1101\/gad.1941310.","journal-title":"Genes Dev"},{"issue":"1","key":"899_CR14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1083\/jcb.201207087","volume":"199","author":"F Rigo","year":"2012","unstructured":"Rigo F, Hua Y, Krainer AR, Bennett CF. Antisense-based therapy for the treatment of spinal muscular atrophy. J Cell Biol. 2012;199(1):21\u20135. https:\/\/doi.org\/10.1083\/jcb.201207087.","journal-title":"J Cell Biol"},{"issue":"10063","key":"899_CR15","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1016\/S0140-6736(16)31408-8","volume":"388","author":"RS Finkel","year":"2016","unstructured":"Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017\u201326. https:\/\/doi.org\/10.1016\/S0140-6736(16)31408-8.","journal-title":"Lancet"},{"issue":"18","key":"899_CR16","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","volume":"377","author":"RS Finkel","year":"2017","unstructured":"Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, ENDEAR Study Group, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377(18):1723\u201332. https:\/\/doi.org\/10.1056\/NEJMoa1702752.","journal-title":"N Engl J Med"},{"issue":"5","key":"899_CR17","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1002\/mus.27187","volume":"63","author":"G Acsadi","year":"2021","unstructured":"Acsadi G, Crawford TO, Muller-Felber W, Shieh PB, Richardson R, Natarajan N, et al. Safety and efficacy of nusinersen in spinal muscular atrophy: the EMBRACE study. Muscle Nerve. 2021;63(5):668\u201377. https:\/\/doi.org\/10.1002\/mus.27187.","journal-title":"Muscle Nerve"},{"issue":"10","key":"899_CR18","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1212\/WNL.0000000000002445","volume":"86","author":"CA Chiriboga","year":"2016","unstructured":"Chiriboga CA, Swoboda KJ, Darras BT, Iannaccone ST, Montes J, De Vivo DC, et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology. 2016;86(10):890\u20137. https:\/\/doi.org\/10.1212\/WNL.0000000000002445.","journal-title":"Neurology"},{"issue":"7","key":"899_CR19","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1056\/NEJMoa1710504","volume":"378","author":"E Mercuri","year":"2018","unstructured":"Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, CHERISH Study Group, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378(7):625\u201335. https:\/\/doi.org\/10.1056\/NEJMoa1710504.","journal-title":"N Engl J Med"},{"issue":"21","key":"899_CR20","doi-asserted-by":"publisher","first-page":"e2492","DOI":"10.1212\/WNL.0000000000007527","volume":"92","author":"BT Darras","year":"2019","unstructured":"Darras BT, Chiriboga CA, Iannaccone ST, Swoboda KJ, Montes J, Mignon L, ISIS-396443-CS2\/ISIS-396443-CS12 Study Groups, et al. Nusinersen in later-onset spinal muscular atrophy: long-term results from the phase 1\/2 studies. Neurology. 2019;92(21):e2492\u2013506. https:\/\/doi.org\/10.1212\/WNL.0000000000007527.","journal-title":"Neurology"},{"issue":"Suppl. 1","key":"899_CR21","doi-asserted-by":"publisher","first-page":"S124","DOI":"10.1016\/j.nmd.2020.08.265","volume":"30","author":"R Finkel","year":"2020","unstructured":"Finkel R, Castro D, Farrar M, Tulinius M, Krosschell K, Saito K, on behalf of the SHINE Study Group, et al. Nusinersen in infantile-onset spinal muscular atrophy: results from longer-term treatment from the open-label SHINE extension study. Neuromuscul Disord. 2020;30(Suppl. 1):S124. https:\/\/doi.org\/10.1016\/j.nmd.2020.08.265.","journal-title":"Neuromuscul Disord"},{"issue":"Suppl. 1","key":"899_CR22","doi-asserted-by":"publisher","first-page":"S121","DOI":"10.1016\/j.nmd.2020.08.257","volume":"30","author":"E Mercuri","year":"2020","unstructured":"Mercuri E, Darras B, Chiriboga C, Farrar M, Kirschner J, Kuntz N, on behalf of the SHINE Study Group, et al. Longer-term treatment with nusinersen: results in later-onset spinal muscular atrophy from the SHINE study. Neuromuscul Disord. 2020;30(Suppl. 1):S121. https:\/\/doi.org\/10.1016\/j.nmd.2020.08.257.","journal-title":"Neuromuscul Disord"},{"issue":"11","key":"899_CR23","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.nmd.2019.09.007","volume":"29","author":"DC De Vivo","year":"2019","unstructured":"De Vivo DC, Bertini E, Swoboda KJ, Hwu WL, Crawford TO, Finkel RS, NURTURE Study Group, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the phase 2 NURTURE study. Neuromuscul Disord. 2019;29(11):842\u201356. https:\/\/doi.org\/10.1016\/j.nmd.2019.09.007.","journal-title":"Neuromuscul Disord"},{"issue":"9","key":"899_CR24","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1007\/s40263-019-00656-w","volume":"33","author":"BT Darras","year":"2019","unstructured":"Darras BT, Farrar MA, Mercuri E, Finkel RS, Foster R, Hughes SG, et al. An integrated safety analysis of infants and children with symptomatic spinal muscular atrophy (SMA) treated with nusinersen in seven clinical trials. CNS Drugs. 2019;33(9):919\u201332. https:\/\/doi.org\/10.1007\/s40263-019-00656-w.","journal-title":"CNS Drugs"},{"issue":"4","key":"899_CR25","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/S1474-4422(20)30037-5","volume":"19","author":"T Hagenacker","year":"2020","unstructured":"Hagenacker T, Wurster CD, G\u00fcnther R, Schreiber-Katz O, Osmanovic A, Petri S, et al. Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Lancet Neurol. 2020;19(4):317\u201325. https:\/\/doi.org\/10.1016\/S1474-4422(20)30037-5.","journal-title":"Lancet Neurol"},{"key":"899_CR26","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.ejpn.2020.05.002","volume":"27","author":"L Szab\u00f3","year":"2020","unstructured":"Szab\u00f3 L, Gergely A, Jakus R, Fogarasi A, Grosz Z, Moln\u00e1r MJ, et al. Efficacy of nusinersen in type 1, 2 and 3 spinal muscular atrophy: real world data from Hungarian patients. Eur J Paediatr Neurol. 2020;27:37\u201342. https:\/\/doi.org\/10.1016\/j.ejpn.2020.05.002.","journal-title":"Eur J Paediatr Neurol"},{"issue":"4","key":"899_CR27","doi-asserted-by":"publisher","first-page":"453","DOI":"10.3233\/JND-190416","volume":"6","author":"MC Walter","year":"2019","unstructured":"Walter MC, Wenninger S, Thiele S, Stauber J, Hiebeler M, Greckl E, et al. Safety and treatment effects of nusinersen in longstanding adult 5q-SMA type 3: a prospective observational study. J Neuromuscul Dis. 2019;6(4):453\u201365. https:\/\/doi.org\/10.3233\/JND-190416.","journal-title":"J Neuromuscul Dis."},{"issue":"3","key":"899_CR28","doi-asserted-by":"publisher","first-page":"e317","DOI":"10.1212\/CPJ.0000000000001033","volume":"11","author":"T Duong","year":"2021","unstructured":"Duong T, Wolford C, McDermott MP, Macpherson CE, Pasternak A, Glanzman AM, et al. Nusinersen treatment in adults with spinal muscular atrophy. Neurol Clin Pract. 2021;11(3):e317\u201327. https:\/\/doi.org\/10.1212\/CPJ.0000000000001033.","journal-title":"Neurol Clin Pract."},{"key":"899_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.650532","volume":"12","author":"B Elsheikh","year":"2021","unstructured":"Elsheikh B, Severyn S, Zhao S, Kline D, Linsenmayer M, Kelly K, et al. Safety, tolerability, and effect of nusinersen in non-ambulatory adults with spinal muscular atrophy. Front Neurol. 2021;12: 650532. https:\/\/doi.org\/10.3389\/fneur.2021.650532.","journal-title":"Front Neurol"},{"key":"899_CR30","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.650535","volume":"12","author":"B Elsheikh","year":"2021","unstructured":"Elsheikh B, Severyn S, Zhao S, Kline D, Linsenmayer M, Kelly K, et al. Safety, tolerability, and effect of nusinersen treatment in ambulatory adults with 5q-SMA. Front Neurol. 2021;12: 650535. https:\/\/doi.org\/10.3389\/fneur.2021.650535.","journal-title":"Front Neurol"},{"issue":"11","key":"899_CR31","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1136\/jnnp-2020-323822","volume":"91","author":"L Maggi","year":"2020","unstructured":"Maggi L, Bello L, Bonanno S, Govoni A, Caponnetto C, Passamano L, et al. Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3. J Neurol Neurosurg Psychiatry. 2020;91(11):1166\u201374. https:\/\/doi.org\/10.1136\/jnnp-2020-323822.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"899_CR32","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.nmd.2021.02.014","volume":"31","author":"D MacCannell","year":"2021","unstructured":"MacCannell D, Berger Z, East L, Mercuri E, Kirschner J, Muntoni F, et al. Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen. Neuromuscul Disord. 2021;31(4):310\u20138. https:\/\/doi.org\/10.1016\/j.nmd.2021.02.014.","journal-title":"Neuromuscul Disord"},{"key":"899_CR33","volume-title":"Elegant graphics for data analysis","author":"H Wickham","year":"2016","unstructured":"Wickham H. Elegant graphics for data analysis. New York (NY): Springer; 2016."},{"issue":"Suppl. 1","key":"899_CR34","doi-asserted-by":"publisher","first-page":"S131","DOI":"10.1016\/j.nmd.2021.07.294","volume":"31","author":"M Ryan","year":"2021","unstructured":"Ryan M, Finkel R, Pascual Pascual S, Day J, Mercuri E, De Vivo D, et al. Scientific rationale for a higher dose of nusinersen. Neuromuscul Disord. 2021;31(Suppl. 1):S131. https:\/\/doi.org\/10.1016\/j.nmd.2021.07.294.","journal-title":"Neuromuscul Disord"}],"container-title":["CNS Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-022-00899-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40263-022-00899-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-022-00899-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T09:24:33Z","timestamp":1645521873000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40263-022-00899-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["899"],"URL":"https:\/\/doi.org\/10.1007\/s40263-022-00899-0","relation":{},"ISSN":["1172-7047","1179-1934"],"issn-type":[{"value":"1172-7047","type":"print"},{"value":"1179-1934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,26]]},"assertion":[{"value":"11 January 2022","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2022","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was sponsored by Biogen. The open access fee was funded by Biogen.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Drew MacCannell, Zdenek Berger, and Marta Valente are full-time employees of and hold stock\/stock options in Biogen. Janbernd Kirschner received funding for consultancy, educational, and research activities concerning SMA from AveXis\/Novartis Gene Therapies, Biogen, Roche, and Scholar Rock. Eugenio Mercuri has participated in advisory boards for SMA studies for AveXis\/Novartis Gene Therapies, Biogen, Ionis, Novartis, and Roche; is a principal investigator for ongoing Biogen\/Ionis and Roche clinical trials; and has received funding from Famiglie SMA Italy, Italian Telethon, and SMA Europe. Michelle A. Farrar has participated in advisory boards for and received honoraria from Biogen, Roche, and Novartis. Susan T. Iannaccone receives partial salary support from the following grants: the Muscular Dystrophy Association, NeuroNEXT U24NS107176, NIH Wellstone Muscular Dystrophy Center P50HD087351, and Taysha Gene Therapies; receives research support from CureSMA, DoD W81XWH2010293, Parent Project for MD, and industry (Biogen, FibroGen, Novartis, PTC, ReveraGen, Sarepta, and Scholar Rock); and has served on medical advisory boards for Biogen, Novartis, and Sarepta. Nancy L. Kuntz has participated in advisory boards for argenx, Audentes, AveXis\/Novartis Gene Therapies, Biogen, Cytokinetics, PTC, Roche, and Sarepta, and received honoraria from Biogen and clinical research funding direct to her institution from Audentes, AveXis\/Novartis Gene Therapies, Biogen, and Sarepta. Richard S. Finkel has participated in SMA advisory boards for AveXis\/Novartis Gene Therapies, Biogen, Roche, and Scholar Rock; received honoraria from AveXis\/Novartis Gene Therapies, Biogen, Elsevier, Excerpta Medica, Roche, and Voyager; received research funding to institution from Biogen and Ionis for conduct of the CS3A, CHERISH, ENDEAR, NURTURE, and SHINE studies, and from AveXis\/Novartis Gene Therapies, Cytokinetics, Roche, and Scholar Rock; was a member of the data safety monitoring boards for the AveXis AVX-101 phase I gene transfer study and the Roche Moonfish phase Ib study; serves in an advisory capacity for the nonprofit organizations Cure SMA, SMA Europe, SMA Foundation, and SMA Reach (UK); and receives royalty payments from the Children\u2019s Hospital of Philadelphia for licensing fees obtained for use of the CHOP INTEND motor function scale. Francesco Muntoni has participated in advisory boards for Biogen, Dyne Therapeutics, and Pfizer; has been a consultant for AveXis\/Novartis Gene Therapies, Biogen, Roche, Santhera, and Sarepta; received grants from the European Commission, Muscular Dystrophy Association USA, Muscular Dystrophy UK, and Medical Research Council; received research funding\/investigator grants from Biogen and Sarepta; and has been a principal investigator for Ionis nusinersen trials, the Roche olesoxime and risdiplam trials in SMA, and the Avexis\/Novartis gene therapy trial of onasemnogene abeparvovec.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The nusinersen clinical trials were conducted in compliance with the Declaration of Helsinki, the International Council for Harmonisation Good Clinical Practice guidelines, and local regulatory requirements.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from the parent or legal guardian and the participant, as required by local guidelines and age, for each clinical trial.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Requests for data supporting this manuscript should be submitted to the Biogen Clinical Data Request Portal (\n                      \n                      ).","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"JK, EM, MAF, STI, NLK, RSF, and FM participated in the collection of data. DM, ZB, and MV participated in the study design and DM conducted the pharmacokinetic analyses. DM, ZB, JK, EM, MAF, STI, NLK, RSF, MV, and FM participated in the analysis and interpretation of data and in drafting and critically revising the manuscript. All authors have read and approved the final submitted paper and agree to be accountable for the work.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}]}}