title: Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy.
abstract: Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON.
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Han
authors.initials: H
authors.lastname: Pei
authors.affiliation: Department of Oncology, Central Hospital, Ezhou City, China.
authors.forename: Min-jian
authors.initials: MJ
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei-kun
authors.initials: WK
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Heng
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Si-qi
authors.initials: SQ
authors.lastname: Ma
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Beijing FivePlus Molecular Medicine Institute Co. Ltd., Beijing, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Dong
authors.affiliation: Center Genetic Diagnosis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center Genetic Diagnosis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dao-wen
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D000229:Dependovirus / Q000235:genetics*; D004596:Electroretinography; D005260:Female; D005500:Follow-Up Studies; D015316:Genetic Therapy / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation; D011239:Prednisolone / Q000008:administration & dosage; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C098483:NADH dehydrogenase subunit 4; D011239:Prednisolone; D009245:NADH Dehydrogenase