{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T09:31:25Z","timestamp":1793266285247,"version":"4.5.0"},"reference-count":31,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Onasemnogene abeparvovec is an adeno-associated virus serotype 9 (AAV9) gene therapy for spinal muscular atrophy (SMA) that is frequently associated with immune-mediated hepatotoxicity. Previous studies have suggested that older age and higher body weight may increase the risk or severity of hepatic enzyme elevation; however, interpretation is limited by heterogeneous immunosuppression strategies across centers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study of children with SMA who received onasemnogene abeparvovec between 2020 and 2025 and were managed using a unified, protocol-driven immunomodulation strategy. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values (upper limit of normal [ULN] 35 U\/L), as well as the timing of peak transaminase elevations, were analyzed in relation to age and weight at infusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 152 children with adequate biochemical follow-up, hepatic enzyme elevation was common: 63.2% had peak ALT \u22652\u00d7 ULN and 29.6% had peak ALT \u22655\u00d7 ULN. Weight demonstrated a statistically significant but modest correlation with peak ALT magnitude (r = 0.184, p = 0.023), whereas age was not associated with transaminase severity. In contrast, age correlated with delayed timing of peak ALT (r = 0.229, p = 0.005) and AST (r = 0.283, p &lt; 0.001). All hepatic enzyme abnormalities resolved under protocol-based immunomodulation, and no cases of hepatic failure or synthetic dysfunction occurred.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>When managed with a structured, proactive immunomodulation protocol, hepatotoxicity following onasemnogene abeparvovec is predictable and manageable. Weight modestly influences ALT severity, while age primarily affects the timing rather than the magnitude of hepatic immune activation, supporting safe administration across a broad pediatric age and weight spectrum.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/22143602261458428","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:43:09Z","timestamp":1780569789000},"page":"1494-1503","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Determinants of hepatic enzyme elevations following onasemnogene abeparvovec: Results from a unified immunomodulation protocol"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9235-2470","authenticated-orcid":false,"given":"Vivek","family":"Mundada","sequence":"first","affiliation":[{"name":"Aster DM Healthcare"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syon","family":"Parashar","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4942-0845","authenticated-orcid":false,"given":"Anil","family":"Dhawan","sequence":"additional","affiliation":[{"name":"Kings College Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-022-00380-8"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S239603"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02455-x"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1060028020914274"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S214174"},{"key":"e_1_3_8_7_2","volume-title":"FDA approves gene therapy for treatment of spinal muscular atrophy","author":"U.S. Food & Drug Administration","unstructured":"U.S. Food & Drug Administration. FDA approves gene therapy for treatment of spinal muscular atrophy. FDA News Release. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-gene-therapy-treatment-spinal-muscular-atrophy (accessed 22 Dec 2025)."},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.10.029"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2023.100817"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51519"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-019-0085-4"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2022.138"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2025.100681"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1159\/000362724"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.4.5454"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(21)00287-X"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101997"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000210268"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.786174"},{"key":"e_1_3_8_20_2","first-page":"221436022513912","article-title":"Onasemnogene abeparvovec gene therapy for treatment of patients with spinal muscular atrophy: updated real-world practical considerations","author":"Proud CM","year":"2025","unstructured":"Proud CM, Kichula EA, Matesanz SE, et al. Onasemnogene abeparvovec gene therapy for treatment of patients with spinal muscular atrophy: updated real-world practical considerations. J Neuromuscul Dis 2025: 22143602251391258. https:\/\/doi.org\/10.1177\/22143602251391258","journal-title":"J Neuromuscul Dis"},{"key":"e_1_3_8_21_2","volume-title":"StatPearls. Treasure Island (FL)","author":"Moriles K","year":"2024","unstructured":"Moriles K, Zubair M, Azer S. Alanine aminotransferase (ALT) test. StatPearls. Treasure Island (FL). StatPearls Publishing, 2024."},{"key":"e_1_3_8_22_2","first-page":"808","article-title":"Onasemnogene abeparvovec gene therapy for spinal muscular atrophy: a cohort study from the United Arab Emirates","volume":"70","author":"Mundada V","year":"2024","unstructured":"Mundada V, Narayan O, Arora S, et al. Onasemnogene abeparvovec gene therapy for spinal muscular atrophy: a cohort study from the United Arab Emirates. Muscle Nerve 2024; 70: 808\u2013815. https:\/\/doi.org\/10.1002\/mus.28222","journal-title":"Muscle Nerve"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-0729"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2024.07.004"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2021.01.012"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2022.05.001"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2012.01.007"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.2217\/ahe.09.69"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(84)90104-0"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.101092"},{"key":"e_1_3_8_31_2","first-page":"100817","article-title":"Long-term Safety of Onasemnogene Abeparvovec for Patients with Spinal Muscular Atrophy: Real-world Findings from the RESTORE Registry","volume":"43","author":"Finkel R","year":"2024","unstructured":"Finkel R, Alecu I, Lopez-Leon S, et al. Long-term Safety of Onasemnogene Abeparvovec for Patients with Spinal Muscular Atrophy: Real-world Findings from the RESTORE Registry. Neuromuscular Disorders 2024; 43: 100817.","journal-title":"Neuromuscular Disorders"},{"key":"e_1_3_8_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedneo.2022.07.006"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/22143602261458428","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/22143602261458428","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/22143602261458428","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:31:51Z","timestamp":1793262711000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/22143602261458428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1177\/22143602261458428"],"URL":"https:\/\/doi.org\/10.1177\/22143602261458428","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]}}}