%0 Journal Article
%A Yu-Wai-Man, Patrick
%A Newman, Nancy J
%A Biousse, Valérie
%A Carelli, Valerio
%A Moster, Mark L
%A Vignal-Clermont, Catherine
%A Klopstock, Thomas
%A Sadun, Alfredo A
%A Sergott, Robert C
%A Hage, Rabih
%A Degli Esposti, Simona
%A La Morgia, Chiara
%A Priglinger, Claudia
%A Karanja, Rustum
%A Taiel, Magali
%A Sahel, José-Alain
%T Five-Year Outcomes of Lenadogene Nolparvovec Gene Therapy in Leber Hereditary Optic Neuropathy.
%J JAMA ophthalmology
%V 143
%N 2
%@ 2168-6165
%C Chicago, Ill.
%I American Medical Association
%M DZNE-2025-00340
%P 99
%D 2025
%X Limited studies have assessed the long-term benefit/risk of gene therapy for Leber hereditary optic neuropathy (LHON).To determine the safety and efficacy of lenadogene nolparvovec in patients with LHON due to the MT-ND4 gene variant for up to 5 years after administration.The RESCUE and REVERSE Long-Term Follow-up Study (RESTORE), conducted from 2018 to 2022, is the 5-year follow-up study of the 2 phase 3 clinical studies RESCUE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss Up to 6 Months From Onset in LHON Due to the MT-ND4 Mutation) and REVERSE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss From 7 Months to 1 Year From Onset in LHON Due to the MT-ND4 Mutation). At the end of each study, ie, 2 years after gene therapy administration, patients were offered enrollment in the RESTORE trial, a multinational, multicenter, prospective study, for an additional 3 years of follow-up. Patients with LHON due to the MT-ND4 gene variant received lenadogene nolparvovec in 1 eye and a sham injection in the other eye.Lenadogene nolparvovec was administered as a single intravitreal injection in the RESCUE/REVERSE studies.Measures included best-corrected visual acuity (BCVA), quality of life using the National Eye Institute visual functioning questionnaire 25 (NEI VFQ-25), and adverse events.Among the 76 patients who received gene therapy in the RESCUE (n = 39) and REVERSE (n = 37) studies, 72 (94.7
%K Optic Atrophy, Hereditary, Leber: genetics
%K Optic Atrophy, Hereditary, Leber: therapy
%K Optic Atrophy, Hereditary, Leber: physiopathology
%K Humans
%K Genetic Therapy: methods
%K Male
%K Visual Acuity: physiology
%K Female
%K Follow-Up Studies
%K Adult
%K Prospective Studies
%K Treatment Outcome
%K NADH Dehydrogenase: genetics
%K Genetic Vectors
%K Young Adult
%K Dependovirus: genetics
%K Adolescent
%K Mutation
%K Middle Aged
%K DNA, Mitochondrial: genetics
%K Quality of Life
%K NADH dehydrogenase subunit 4 (NLM Chemicals)
%K NADH Dehydrogenase (NLM Chemicals)
%K DNA, Mitochondrial (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39699886
%2 pmc:PMC11843360
%R 10.1001/jamaophthalmol.2024.5375
%U https://pub.dzne.de/record/276827