TY  - JOUR
AU  - Yu-Wai-Man, Patrick
AU  - Newman, Nancy J
AU  - Biousse, Valérie
AU  - Carelli, Valerio
AU  - Moster, Mark L
AU  - Vignal-Clermont, Catherine
AU  - Klopstock, Thomas
AU  - Sadun, Alfredo A
AU  - Sergott, Robert C
AU  - Hage, Rabih
AU  - Degli Esposti, Simona
AU  - La Morgia, Chiara
AU  - Priglinger, Claudia
AU  - Karanja, Rustum
AU  - Taiel, Magali
AU  - Sahel, José-Alain
TI  - Five-Year Outcomes of Lenadogene Nolparvovec Gene Therapy in Leber Hereditary Optic Neuropathy.
JO  - JAMA ophthalmology
VL  - 143
IS  - 2
SN  - 2168-6165
CY  - Chicago, Ill.
PB  - American Medical Association
M1  - DZNE-2025-00340
SP  - 99
PY  - 2025
AB  - 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
KW  - Optic Atrophy, Hereditary, Leber: genetics
KW  - Optic Atrophy, Hereditary, Leber: therapy
KW  - Optic Atrophy, Hereditary, Leber: physiopathology
KW  - Humans
KW  - Genetic Therapy: methods
KW  - Male
KW  - Visual Acuity: physiology
KW  - Female
KW  - Follow-Up Studies
KW  - Adult
KW  - Prospective Studies
KW  - Treatment Outcome
KW  - NADH Dehydrogenase: genetics
KW  - Genetic Vectors
KW  - Young Adult
KW  - Dependovirus: genetics
KW  - Adolescent
KW  - Mutation
KW  - Middle Aged
KW  - DNA, Mitochondrial: genetics
KW  - Quality of Life
KW  - NADH dehydrogenase subunit 4 (NLM Chemicals)
KW  - NADH Dehydrogenase (NLM Chemicals)
KW  - DNA, Mitochondrial (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39699886
C2  - pmc:PMC11843360
DO  - DOI:10.1001/jamaophthalmol.2024.5375
UR  - https://pub.dzne.de/record/276827
ER  -