Abstract | BACKGROUND: Delandistrogene moxeparvovec is a gene transfer therapy approved in the United States, United Arab Emirates, and Qatar for the treatment of ambulatory patients aged four through five years with a confirmed Duchenne muscular dystrophy (DMD)-causing mutation in the DMD gene. This therapy was developed to address the underlying cause of DMD through targeted skeletal, respiratory, and cardiac muscle expression of delandistrogene moxeparvovec micro- dystrophin, an engineered, functional dystrophin protein. METHODS: Drawing on clinical trial experience from Study 101 (NCT03375164), Study 102 (NCT03769116), and ENDEAVOR (Study 103; NCT04626674), we outline practical considerations for delandistrogene moxeparvovec treatment. RESULTS: Before infusion, the following are recommended: (1) screen for anti-adeno-associated virus rhesus isolate serotype 74 total binding antibody titers <1:400; (2) assess liver function, platelet count, and troponin-I; (3) ensure patients are up to date with vaccinations and avoid vaccine coadministration with infusion; (4) administer additional corticosteroids starting one day preinfusion (for patients already on corticosteroids); and (5) postpone dosing patients with any infection or acute liver disease until event resolution. Postinfusion, the following are recommended: (1) monitor liver function weekly (three months postinfusion) and, if indicated, continue until results are unremarkable; (2) monitor troponin-I levels weekly (first month postinfusion, continuing if indicated); (3) obtain platelet counts weekly (two weeks postinfusion), continuing if indicated; and (4) maintain the corticosteroid regimen for at least 60 days postinfusion, unless earlier tapering is indicated. CONCLUSIONS: Although the clinical safety profile of delandistrogene moxeparvovec has been consistent, monitorable, and manageable, these practical considerations may mitigate potential risks in a real-world clinical practice setting.
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Authors | Jerry R Mendell, Crystal Proud, Craig M Zaidman, Stefanie Mason, Eddie Darton, Shufang Wang, Christoph Wandel, Alexander P Murphy, Eugenio Mercuri, Francesco Muntoni, Craig M McDonald |
Journal | Pediatric neurology
(Pediatr Neurol)
Vol. 153
Pg. 11-18
(Apr 2024)
ISSN: 1873-5150 [Electronic] United States |
PMID | 38306745
(Publication Type: Journal Article)
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Copyright | Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Dystrophin
- Troponin I
- Adrenal Cortex Hormones
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Topics |
- Humans
- Muscular Dystrophy, Duchenne
(genetics, therapy)
- Dystrophin
(genetics, metabolism, therapeutic use)
- Troponin I
(genetics, metabolism)
- Adrenal Cortex Hormones
(therapeutic use)
- Genetic Therapy
- Muscle, Skeletal
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