Abstract
Purpose :
To evaluate the safety and efficacy of a recombinant adeno-associated virus serotype 2 (rAAV2) carrying normal ND4 (rAAV2-ND4) (NR082) in participants with visual loss from Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A mutation, and explore a safe dose of NR082 intravitreal injection.
Methods :
12 participants with the m.11778G>A mitochondrial DNA mutation and vision loss more than 6 months from onset in both eyes were included in this prospective open-label trial. They were treated with intravitreally injection unilaterally, the first 6 participants were treated at the initial dose of vector (1.5*109 vg, 0.05mL) (Group I), and the other 6 participants were treated at the high dose (4.5*109 vg, 0.05mL) (Group II). Treated participants were followed for 52 weeks and underwent ocular and systemic safety assessments along with visual structure and function examinations.
Results :
A total of 12 participants were included in this study, 5 male subjects and 1 female in Group I with a mean age of 19.0 ± 1.55 years and 21.8 ± 5.27 years in Group II. The baseline BCVA in the injected eyes in Group I was 1.89 ± 0.36 logMAR, which improved to 1.59 ± 0.10 logMAR at week 52nd after intravitreal rAAV2-ND4. In Group II, the baseline BCVA in the injected eyes was 2.20 ± 0.15 logMAR, and BCVA at week 52nd after treatment was 1.92 ± 0.32 logMAR. There were three and four injected eyes improved significantly after 52-week's follow-up in Group I and Group II respectively. There was no serious ocular or systemic adverse events or dose-limiting toxicity in all participants. The adverse events possibly related to the treatment included uveitis, vitreous opacity and keratic precipitates.
Conclusions :
No serious safety problems were observed in the 12 participants enrolled in this phase 1/2 trial of virus-based gene transfer in this mitochondrial disorder. Additional study follow-up of these and additional participants is needed to confirm these preliminary observations.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.