{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:40:27Z","timestamp":1790991627252,"version":"4.1.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Spinal muscular atrophy (SMA) is caused by deletions or mutations in the survival of motor neuron (SMN) 1 gene resulting in progressive motor function loss, and additional disease-related complications, including dysphagia and respiratory failure. With three US FDA\u2013approved disease-modifying therapies (DMTs) available for SMA, patients, caregivers and healthcare providers have become increasingly interested in using a combination of DMTs to maximize clinical benefit. Current data on combination therapy are limited, and additional studies are needed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentation<\/jats:title>\n            <jats:p>This multicenter, retrospective case series presents real-world outcomes in children with SMA who received onasemnogene abeparvovec (OA; ZOLGENSMA<jats:sup>\u00ae<\/jats:sup>), a single-dose gene therapy, and were subsequently treated with risdiplam (EVRYSDI<jats:sup>\u00ae<\/jats:sup>), a once-daily oral DMT. Adverse events as well as motor, respiratory and swallowing outcomes were evaluated before and after risdiplam initiation.<\/jats:p>\n            <jats:p>Twenty children were included, ten (50%) of whom were female. The majority had Type 1 SMA (<jats:italic>n<\/jats:italic>\u2009=\u200917; 85%) and two <jats:italic>SMN2<\/jats:italic> copies (<jats:italic>n<\/jats:italic>\u2009=\u200916; 80%). At baseline, eight (40%) children were clinically diagnosed with severe dysphagia, and ten (50%) required either noninvasive ventilation or invasive ventilation via tracheostomy. The mean time from OA administration to risdiplam initiation was 15.2\u00a0months, and the mean age at risdiplam initiation was 24.9\u00a0months. The most common reasons (<jats:italic>n<\/jats:italic>\u2009=\u200915; 75%) for starting risdiplam were either a plateau or inadequate improvement in disease symptoms. After risdiplam initiation, seven (35%) and six (30%) children had improvements in swallowing and respiratory function, respectively. Of the children whose motor function was assessed with the Children\u2019s Hospital of Philadelphia Infant Test of Neuromuscular Disorders and\/or the Hammersmith Functional Motor Scale\u00a0\u2013\u00a0Expanded after risdiplam initiation, nearly all (<jats:italic>n<\/jats:italic>\u2009=\u200912\/13; 92%) showed stability or improvement. No serious adverse events were observed post risdiplam initiation, and one child discontinued risdiplam due to a perceived lack of effectiveness.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Many children included in this case series had improvements in motor, respiratory and\/or bulbar function after adding risdiplam following OA. No new safety concerns were observed. The real-world evidence generated from this case series provides additional information on risdiplam\u2019s risk\u2013benefit profile after OA administration in children with SMA. Future studies with a larger cohort should be conducted.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s12883-025-04276-4","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T02:13:52Z","timestamp":1751854432000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Risdiplam treatment following onasemnogene abeparvovec in individuals with spinal muscular atrophy: a multicenter case series"],"prefix":"10.1186","volume":"25","author":[{"given":"Melissa D.","family":"Svoboda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Kuntz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Leon-Astudillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jena","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Sieburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"4276_CR1","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/B978-0-323-37101-8.00139-9","volume-title":"Swaiman's Pediatric Neurology: Principles and Practice","author":"B Darras","year":"2017","unstructured":"Darras B, Monani U, De Vivo D. Genetic disorders affecting the motor neuron: spinal muscular atrophy. In: Swaiman K, Ashwal S, Ferriero D, Schor N, Finkel R, Gropman A, Pearl P, editors. Swaiman\u2019s Pediatric Neurology: Principles and Practice. 6th ed. Shevell M: Elsevier; 2017. p. 1057\u201364.","edition":"6"},{"key":"4276_CR2","doi-asserted-by":"publisher","first-page":"7341","DOI":"10.2147\/IJGM.S369021","volume":"15","author":"L Ramos-Platt","year":"2022","unstructured":"Ramos-Platt L, Elman L, Shieh PB. Experience and perspectives in the US on the evolving treatment landscape in spinal muscular atrophy. Int J Gen Med. 2022;15:7341\u201353.","journal-title":"Int J Gen Med"},{"key":"4276_CR3","first-page":"39","volume":"10","author":"M Jedrzejowska","year":"2020","unstructured":"Jedrzejowska M. Advances in newborn screening and presymptomatic diagnosis of spinal muscular atrophy. Degener Neurol Neuromuscul Dis. 2020;10:39\u201347.","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"4276_CR4","unstructured":"US FDA. SPINRAZATM (nusinersen) package insert. 2016. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/209531lbl.pdf. Accessed on 30 Jun 2025."},{"key":"4276_CR5","unstructured":"US FDA. ZOLGENSMATM (onasemnogene abeparvovec-xioi) package insert. 2019. https:\/\/www.fda.gov\/media\/126109\/download. Accessed on 30 Jun 2025"},{"key":"4276_CR6","unstructured":"US FDA. EVRYSDI\u2122 (risdiplam) package insert. 2020. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/213535s000lbl.pdf. Accessed on 30 Jun 2025."},{"issue":"19","key":"4276_CR7","doi-asserted-by":"publisher","first-page":"14873","DOI":"10.3390\/ijms241914873","volume":"24","author":"I Angilletta","year":"2023","unstructured":"Angilletta I, Ferrante R, Giansante R, Lombardi L, Babore A, Dell\u2019Elice A, Alessandrelli E, Notarangelo S, Ranaudo M, Palmarini C, et al. Spinal muscular atrophy: an evolving scenario through new perspectives in diagnosis and advances in therapies. Int J Mol Sci. 2023;24(19):14873.","journal-title":"Int J Mol Sci"},{"issue":"6","key":"4276_CR8","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1002\/acn3.51560","volume":"9","author":"JM Kwon","year":"2022","unstructured":"Kwon JM, Arya K, Kuntz N, Phan HC, Sieburg C, Swoboda KJ, Veerapandiyan A, Assman B, Bader-Weder S, Dickendesher TL, et al. An expanded access program of risdiplam for patients with Type 1 or 2 spinal muscular atrophy. Ann Clin Transl Neurol. 2022;9(6):810\u20138.","journal-title":"Ann Clin Transl Neurol"},{"issue":"4","key":"4276_CR9","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1002\/mus.27375","volume":"64","author":"KF Oechsel","year":"2021","unstructured":"Oechsel KF, Cartwright MS. Combination therapy with onasemnogene and risdiplam in spinal muscular atrophy type 1. Muscle Nerve. 2021;64(4):487\u201390.","journal-title":"Muscle Nerve"},{"key":"4276_CR10","unstructured":"Arya K, Veerapandiyan A, Drake P, Pomerantz GN, Burnette W, Stefans V, Agarwal A. Clinical efficacy and safety of risdiplam use as combination therapy in spinal muscular atrophy (SMA) patients post onasemnogene-abeparvovec-xioi (onasemnogene) and\/or nusinersen. Oral presentation. 2021 Virtual Cure SMA Research & Clinical Care Meeting. 2021."},{"issue":"8","key":"4276_CR11","doi-asserted-by":"publisher","first-page":"4871","DOI":"10.1007\/s00415-024-12318-z","volume":"271","author":"CA Chiriboga","year":"2024","unstructured":"Chiriboga CA, Bruno C, Duong T, Fischer D, Mercuri E, Kirschner J, Kostera-Pruszczyk A, Jaber B, Gorni K, Kletzl H, et al. JEWELFISH: 24-month results from an open-label study in non-treatment-na\u00efve patients with SMA receiving treatment with risdiplam. J Neurol. 2024;271(8):4871\u201384.","journal-title":"J Neurol"},{"issue":"3","key":"4276_CR12","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.nmd.2009.11.014","volume":"20","author":"AM Glanzman","year":"2010","unstructured":"Glanzman AM, Mazzone E, Main M, Pelliccioni M, Wood J, Swoboda KJ, Scott C, Pane M, Messina S, Bertini E, et al. The Children\u2019s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability. Neuromuscul Disord. 2010;20(3):155\u201361.","journal-title":"Neuromuscul Disord"},{"issue":"9\u201310","key":"4276_CR13","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.nmd.2007.05.009","volume":"17","author":"JM O'Hagen","year":"2007","unstructured":"O\u2019Hagen JM, Glanzman AM, McDermott MP, Ryan PA, Flickinger J, Quigley J, Riley S, Sanborn E, Irvine C, Martens WB, et al. An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients. Neuromuscul Disord. 2007;17(9\u201310):693\u20137.","journal-title":"Neuromuscul Disord"},{"issue":"6","key":"4276_CR14","doi-asserted-by":"publisher","first-page":"fcac269","DOI":"10.1093\/braincomms\/fcac269","volume":"4","author":"FEV Scheijmans","year":"2022","unstructured":"Scheijmans FEV, Cuppen I, van Eijk RPA, Wijngaarde CA, Schoenmakers M, van der Woude DR, Bartels B, Veldhoen ES, Oude Lansink ILB, Groen EJN, et al. Population-based assessment of nusinersen efficacy in children with spinal muscular atrophy: a 3-year follow-up study. Brain Commun. 2022;4(6):fcac269.","journal-title":"Brain Commun"},{"issue":"5","key":"4276_CR15","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1002\/mus.25148","volume":"54","author":"ET Kruitwagen-Van Reenen","year":"2016","unstructured":"Kruitwagen-Van Reenen ET, Wadman RI, Visser-Meily JM, van den Berg LH, Schr\u00f6der C, van der Pol WL. Correlates of health related quality of life in adult patients with spinal muscular atrophy. 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Accessed 30 Jun 2025."}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-025-04276-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-025-04276-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-025-04276-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T01:11:05Z","timestamp":1757207465000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-025-04276-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,7]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4276"],"URL":"https:\/\/doi.org\/10.1186\/s12883-025-04276-4","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,7]]},"assertion":[{"value":"17 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2025","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article has been updated to amend the license information.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Institutional review board approval was obtained or waived from the following institutions:1. Baylor College of Medicine\/CHRISTUS Children\u2019s Hospital (San Antonio, TX): the Baylor College of Medicine IRB approval was obtained and informed consent was provided by the parents or legal guardians.2. University of Florida College of Medicine (Gainesville, FL): University of Florida IRB waived consent. Consent for release of records were\u00a0obtained from caregivers.3. Helen DeVos Children\u2019s Hospital (Grand Rapids, MI): Corewell Health IRB approval (REF #2023\u2013047) and ICF\/HIPPA wavier was obtained.4. Ann & Robert H. Lurie Children\u2019s Hospital of Chicago\/Northwestern University Feinberg School of Medicine (Chicago, IL): Northwestern University IRB approval (REF #2022\u20135667) and informed consent was obtained from the parents or legal guardians.5. University of Wisconsin-Madison School of Medicine and Public Health (Madison, WI): the University of Wisconsin-Madison IRB waived consent.6. Neurology Rare Disease Center (Denton, TX): the institution granted the study exemption from IRB review. Informed consent was obtained from the parents or legal guardians.All methods and procedures were carried out in accordance with relevant guidelines and regulations. Furthermore, the study also adheres to the 2013 Helsinki Declarations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MDS participates in registry studies with Novartis and Genentech and a clinical study with Biohaven; NK serves on medical advisory boards for Argenx, Astellas, Biogen, BioMarin, FibroGen, Genentech, Novartis and Sarepta and has received compensation for educational talks on gene therapy from Sarepta; JK is a principal site investigator for clinical trials sponsored by\u00a0Novartis, Biohaven, FibroGen, Genentech and Scholar Rock and serves on medical advisory boards for Astellas. JMK is a principal site investigator for sponsored clinical trials by\u00a0Novartis and Scholar Rock in SMA; DC has received funding from Genentech, ReveraGen, Edgewise and Biohaven and consulting fees from Arugula Science; CL-A, BB and CS declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"283"}}