دورية أكاديمية
Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy
| العنوان: | Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy |
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| المؤلفون: | Newman, Nancy J., Yu-Wai-Man, Patrick, Subramanian, Prem S., Moster, Mark L., Wang, An-Guor, Donahue, Sean P., Leroy, Bart, Carelli, Valerio, Biousse, Valerie, Vignal-Clermont, Catherine, Sergott, Robert C., Sadun, Alfredo A., Fernandez, Gema Rebolleda, Chwalisz, Bart K., Banik, Rudrani, Bazin, Fabienne, Roux, Michel, Cox, Eric D., Taiel, Magali, Sahel, Jose-Alain, Study Grp, LHON REFLECT |
| المصدر: | BRAIN ; ISSN: 0006-8950 ; ISSN: 1460-2156 |
| بيانات النشر: | Oxfor Univ. Press |
| سنة النشر: | 2023 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, Biology and Life Sciences, lenadogene nolparvovec, leber hereditary optic neuropathy, mitochondrial, DNA, NADH dehydrogenase 4, recombinant adeno-associated virus vector 2, FIBER LAYER EVALUATION, NERVE-FIBER, COMPLEX-I, COHERENCE TOMOGRAPHY, VISUAL FUNCTION, GANGLION-CELL, END-POINTS, BIODISTRIBUTION, EXPRESSION, MUTATIONS |
| الوصف: | Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G>A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/01H2APQR5ZC0W1HHXGJ08XZKECTest; http://hdl.handle.net/1854/LU-01H2APQR5ZC0W1HHXGJ08XZKECTest; http://doi.org/10.1093/brain/awac421Test; https://biblio.ugent.be/publication/01H2APQR5ZC0W1HHXGJ08XZKEC/file/01H2AQ39HRS2ENGMFK27ZY4WHBTest |
| DOI: | 10.1093/brain/awac421 |
| الإتاحة: | https://doi.org/10.1093/brain/awac421Test https://biblio.ugent.be/publication/01H2APQR5ZC0W1HHXGJ08XZKECTest http://hdl.handle.net/1854/LU-01H2APQR5ZC0W1HHXGJ08XZKECTest https://biblio.ugent.be/publication/01H2APQR5ZC0W1HHXGJ08XZKEC/file/01H2AQ39HRS2ENGMFK27ZY4WHBTest |
| حقوق: | Creative Commons Attribution-NonCommercial 4.0 International Public License (CC BY-NC 4.0) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.AF98F39 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/brain/awac421 |
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