{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:00:05Z","timestamp":1788631205663,"version":"build-2803163510"},"reference-count":33,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["UL1 TR000445"],"award-info":[{"award-number":["UL1 TR000445"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"abstract":"<jats:p>Delandistrogene moxeparvovec-rokl (DMR) is the only U.S. Food and Drug Administration-approved gene therapy for patients with Duchenne muscular dystrophy (DMD). After reports of two deaths due to acute liver injury (ALI)\/acute liver failure, our center began prophylaxis with sirolimus to help prevent ALI. The objective of this study is to report the initial safety, tolerability, and efficacy of sirolimus prophylaxis. The clinical course of patients receiving sirolimus prophylaxis with a target trough of 4\u20136 ng\/mL was retrospectively evaluated and compared with those who did not receive sirolimus. Laboratory testing, particularly gamma glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and total bilirubin, was collected. A Fisher\u2019s exact test was used to assess the difference between groups. Twelve patients were started on sirolimus prophylaxis, 10 prior to DMR infusion and 2 within 2 weeks of DMR. The median age at DMR dosing was 11 years old (interquartile range = 8.5\u201314); 11 patients were ambulatory. No patients experienced a serious adverse event related to sirolimus administration. Seven patients developed elevated triglyceride or cholesterol levels and began omega-3 supplementation. None of the patients receiving sirolimus prophylaxis experienced ALI compared with 3 of the 14 patients (21%) infused prior to implementation of the sirolimus protocol. Sirolimus prophylaxis appears to be safe and well-tolerated in DMD patients receiving DMR. While not statistically significant, these results suggest that further study of sirolimus prophylaxis is warranted.<\/jats:p>","DOI":"10.1177\/10430342261472609","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T07:07:36Z","timestamp":1785913656000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety, Tolerability, and Efficacy of a Prophylactic Sirolimus Protocol for Patients Receiving Delandistrogene Moxeparvovec-Rokl Gene Therapy"],"prefix":"10.1177","author":[{"given":"Zahraa","family":"Siddiqui","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Neumann","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Guillen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchee","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Cox","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Bryan","family":"Burnette","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nemours Children\u2019s Health, Jacksonville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9194-5330","authenticated-orcid":false,"given":"Jonathan H.","family":"Soslow","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32910-1"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30024-3"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01430-8"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22097"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.015151"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000214014"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-230185"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27955"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03304-z"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.10.015"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/01926233231201408"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2024.11.005"},{"key":"e_1_3_3_14_1","unstructured":"13.FDA. FDA Approves New Safety Warning and Revised Indication that Limits Use for Elevidys Following Reports of Fatal Liver Injury. FDA; 2025. Available from: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-new-safety-warning-and-revised-indication-limits-use-elevidys-following-reports-fatal"},{"key":"e_1_3_3_15_1","unstructured":"14.Businesswire. Sarepta Announces FDA\u2019s Approval of Updated ELEVIDYS Prescribing Information. Businesswire; 2025. Available from: https:\/\/www.businesswire.com\/news\/home\/20251114275201\/en\/"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/10430342261423168"},{"key":"e_1_3_3_17_1","unstructured":"16.FDA. ELEVIDYS (delandistrogene moxeparvovec-rokl) suspension for intravenous infusion. FDA; 2025. Available from: https:\/\/www.fda.gov\/media\/184855\/download?attachment"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2025.09.003"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2025.100681"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2214084"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(25)00380-3"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/22143602241303357"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811892115"},{"key":"e_1_3_3_24_1","unstructured":"23.Services UDoHaH. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. U.S. Department of Health and Human Services (HHS); 2017. Available from: https:\/\/dctd.cancer.gov\/research\/ctep-trials\/for-sites\/adverse-events\/ctcae-v5-5x7.pdf"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-023-00423-z"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2021.258"},{"key":"e_1_3_3_27_1","first-page":"221436022614249","article-title":"Sirolimus for the treatment of steroid-refractory hepatotoxicity following AAV gene therapy in patients with Duchenne muscular dystrophy","author":"Leon-Astudillo C","year":"2026","unstructured":"26.Leon-Astudillo C, , Salabarria SM, , Chadwick CB, et al. Sirolimus for the treatment of steroid-refractory hepatotoxicity following AAV gene therapy in patients with Duchenne muscular dystrophy. J Neuromuscul Dis 2026:22143602261424971.","journal-title":"J Neuromuscul Dis"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.07.016"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307952"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI173510"},{"key":"e_1_3_3_31_1","unstructured":"30.East LMS Darton E Griffin DA et al. Model-Based Evaluation of Delandistrogene Moxeparvovec Adeno-Associated Virus Pharmacokinetics and Safety Implications. Muscular Dystrophy Association (MDA); 2026. Available from: https:\/\/www.mdaconference.org\/abstract-library\/model-based-evaluation-of-delandistrogene-moxeparvovec-adeno-associated-virus-pharmacokinetics-and-safety-implications\/"},{"key":"e_1_3_3_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2026.01.004"},{"key":"e_1_3_3_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/01926233241298892"},{"key":"e_1_3_3_34_1","unstructured":"33.Sarepta Therapeutics I. Sarepta Announces that Screening and Enrollment are Underway in ENDEAVOR Cohort 8 to Evaluate Enhanced Immunosuppression Regimen as Part of ELEVIDYS Gene Therapy for Non-Ambulant Individuals with Duchenne. Sarepta Therapeutics Inc; 2026. Available from: https:\/\/investorrelations.sarepta.com\/news-releases\/news-release-details\/sarepta-announces-screening-and-enrollment-are-underway-endeavor"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10430342261472609","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10430342261472609","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10430342261472609","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T17:51:26Z","timestamp":1786038686000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10430342261472609"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":33,"alternative-id":["10.1177\/10430342261472609"],"URL":"https:\/\/doi.org\/10.1177\/10430342261472609","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"article-number":"10430342261472609"}}