{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:16:09Z","timestamp":1793103369807,"version":"4.5.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gene Ther"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Supported by encouraging trial outcomes, onasemnogene abeparvovec (OA) was authorized for spinal muscular atrophy (SMA). Nevertheless, efficacy of OA in advanced SMA patients remains underexplored. This investigation assessed clinical effectiveness and adverse effects of OA in a cohort including advanced SMA, and compared to historical survival data for SMA type 1 patients in Thailand. We conducted observational cohort study at Siriraj Hospital, Thailand, from May 2019 to April 2022. The study enrolled eight SMA patients receiving OA therapy. The cohort comprised five SMA type 1 patients treated at 16.7 months (6.5\u201324.9 months) and three SMA type 2 patients treated at 20.3 months (19\u201331.5 months). Before receiving OA, all Type 1 patients required 24-hour invasive ventilation and feeding support. Post-treatment, Three of five showed gradual improvement in motor scores, but none achieved new motor milestones. Survival rate was not improved, with all experiencing fatalities. Conversely, Type 2 patients exhibited motor score improvement without serious adverse events. OA did not significantly improve clinical outcomes or survival rates in advanced Type 1 SMA. These findings highlight need for additional caution when administering OA to severe SMA Type 1 and more specific guidelines in selecting subgroups for treatment.<\/jats:p>","DOI":"10.1038\/s41434-025-00535-8","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T14:10:57Z","timestamp":1745417457000},"page":"553-560","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Fatal outcomes following onasemnogene abeparvovec in advanced-stage spinal muscular atrophy"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9161-4491","authenticated-orcid":false,"given":"Peerada","family":"Pongsakornkullachart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9406-8481","authenticated-orcid":false,"given":"Pimchanok","family":"Kulsirichawaroj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratcharin","family":"Kongkasuwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-9930","authenticated-orcid":false,"given":"Prakarn","family":"Tovichien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Settapong","family":"Jitwongwai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supaluck","family":"Kanjanauthai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nutnicha","family":"Preeprem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivaporn","family":"Limpaninlachat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisasri","family":"Sermpon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4557-0387","authenticated-orcid":false,"given":"Oranee","family":"Sanmaneechai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"535_CR1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/s41572-022-00380-8","volume":"8","author":"E Mercuri","year":"2022","unstructured":"Mercuri E, Sumner CJ, Muntoni F, Darras BT, Finkel RS. Spinal muscular atrophy. Nat Rev Dis Primers. 2022;8:52.","journal-title":"Nat Rev Dis Primers"},{"key":"535_CR2","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1212\/WNL.0000000000000741","volume":"83","author":"RS Finkel","year":"2014","unstructured":"Finkel RS, McDermott MP, Kaufmann P, Darras BT, Chung WK, Sproule DM, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014;83:810\u20137.","journal-title":"Neurology"},{"key":"535_CR3","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, et al. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. N Engl J Med. 2018;378:625\u201335.","journal-title":"N Engl J Med"},{"key":"535_CR4","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/dmcn.14027","volume":"61","author":"T Gidaro","year":"2019","unstructured":"Gidaro T, Servais L. Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps. Dev Med Child Neurol. 2019;61:19\u201324.","journal-title":"Dev Med Child Neurol"},{"key":"535_CR5","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","volume":"377","author":"JR Mendell","year":"2017","unstructured":"Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017;377:1713\u201322.","journal-title":"N Engl J Med"},{"key":"535_CR6","doi-asserted-by":"crossref","unstructured":"Messina S, Sframeli M. New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges. J Clin Med. 2020;9:2222.","DOI":"10.3390\/jcm9072222"},{"key":"535_CR7","doi-asserted-by":"publisher","first-page":"6501","DOI":"10.1021\/acs.jmedchem.8b00741","volume":"61","author":"H Ratni","year":"2018","unstructured":"Ratni H, Ebeling M, Baird J, Bendels S, Bylund J, Chen KS, et al. Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 (SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA). J Med Chem. 2018;61:6501\u201317.","journal-title":"J Med Chem"},{"key":"535_CR8","doi-asserted-by":"publisher","first-page":"11021","DOI":"10.1021\/acs.jmedchem.8b01291","volume":"61","author":"AK Cheung","year":"2018","unstructured":"Cheung AK, Hurley B, Kerrigan R, Shu L, Chin DN, Shen Y, et al. Discovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA). J Med Chem. 2018;61:11021\u201336.","journal-title":"J Med Chem"},{"key":"535_CR9","unstructured":"Zolgensma prescribing information [database on the Internet] 2019 [cited November 2020]. Available from: https:\/\/www.novartis.com\/us-en\/sites\/novartis_us\/files\/zolgensma.pdf."},{"key":"535_CR10","doi-asserted-by":"crossref","unstructured":"Hoy, SM. Onasemnogene Abeparvovec: First Global Approval. Drugs. 2019;79:1255\u201362.","DOI":"10.1007\/s40265-019-01162-5"},{"key":"535_CR11","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ejpn.2024.06.001","volume":"51","author":"J Kirschner","year":"2024","unstructured":"Kirschner J, Bernert G, Butoianu N, De Waele L, Fattal-Valevski A, Haberlova J, et al. 2024 update: European consensus statement on gene therapy for spinal muscular atrophy. 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Additionally, the authors received neither any funding from Novartis as part of this Managed Access Program (MAP). OS served on Novartis\u2019 speaker\u2019s bureau and research grant for a prospective observational SMA cohort in Thailand. The other authors declare that they have no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study protocol was approved by the Siriraj Institutional Review Board (Si 405\/2022), also the historical comparator data was approved by the Siriraj Institutional Review Board (Si 860\/2021), and the research was conducted in accordance with the principles of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}