{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:40:26Z","timestamp":1790991626665,"version":"4.1.0"},"reference-count":29,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:p>Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder arising from biallelic non-functional survival motor neuron 1 (SMN1) genes with variable copies of partially functional SMN2 gene. Intrathecal onasemnogene abeparvovec administration, at fixed, low doses, may enable treatment of heavier patients ineligible for weight-based intravenous dosing. Objective: STRONG (NCT03381729) assessed the safety\/tolerability and efficacy of intrathecal onasemnogene abeparvovec for sitting, nonambulatory SMA patients. Methods: Sitting, nonambulatory SMA patients (biallelic SMN1 loss, three SMN2 copies, aged 6\u2013&lt;60 months) received a single dose of intrathecal onasemnogene abeparvovec. Patients were enrolled sequentially into one of three (low, medium, and high) dose cohorts and stratified into two groups by age at dosing: younger (6\u2013&lt;24 months) and older (24\u2013&lt;60 months). Primary endpoints included safety\/tolerability, independent standing \u22653 seconds (younger group), and change in Hammersmith Functional Motor Scale Expanded (HFMSE) from baseline (older group) compared with historic controls. Results: Thirty-two patients were enrolled and completed the study (medium dose, n\u200a=\u200a25). All patients had one or more treatment-emergent adverse events, with one serious and related to treatment (transaminase elevations). No deaths were reported. One of 13 patients (7.7%) in the younger group treated with the medium dose achieved independent standing. At Month 12 for the older group receiving the medium dose, change from baseline in HFMSE was significantly improved compared with the SMA historic control population (P\u200a&lt;\u200a0.01). Conclusions: Intrathecal onasemnogene abeparvovec was safe and well-tolerated. Older patients treated with the medium dose demonstrated increases in HFMSE score greater than commonly observed in natural history.<\/jats:p>","DOI":"10.3233\/jnd-221560","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T12:29:04Z","timestamp":1678451344000},"page":"389-404","source":"Crossref","is-referenced-by-count":68,"title":["Intrathecal Onasemnogene Abeparvovec for Sitting, Nonambulatory Patients with Spinal Muscular Atrophy: Phase I Ascending-Dose Study (STRONG)"],"prefix":"10.1177","volume":"10","author":[{"given":"Richard S.","family":"Finkel","sequence":"first","affiliation":[{"name":"Center for Experimental Neurotherapeutics, St. Jude Children\u2019s Research Hospital, Memphis, TN, USA"},{"name":"Division of Neurology, Nemours Children\u2019s Hospital, Orlando, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil T.","family":"Darras","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry R.","family":"Mendell","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, Nationwide Children\u2019s Hospital, Columbus, OH, USA"},{"name":"Department of Pediatrics and Department of Neurology, The Ohio State University,Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Neurology, Stanford University Medical Center, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Kuntz","sequence":"additional","affiliation":[{"name":"Division of Neurology, Ann and Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, Nationwide Children\u2019s Hospital, Columbus, OH, USA"},{"name":"Department of Pediatrics and Department of Neurology, The Ohio State University,Columbus, OH, USA"},{"name":"Division of Neurology, Nationwide Children\u2019s Hospital, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"Zaidman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Pediatric Neurology,Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 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