The rAAV2-ND1 gene therapy for Leber hereditary optic neuropathy.

Purpose: No effective treatment for leber hereditary optic neuropathy (LHON) caused by ND1 mutation is available.This study evaluated the safety and efficacy of a single unilateral intravitreal injection rAAV2-ND1 in various doses for the treatment of LHON.

Methods: Twelve patients with LHON (ND1 mutation) in two groups with six participants each.The low-dose group received injection of rAAV2-ND1 in a dose of 1.5 × 10⁸ vg/eye while the high-dose group received 1.5 × 10⁹ vg/eye.The safety endpoint was the incidence of adverse events (AEs).The primary efficacy endpoint was changes of best corrected visual acuity (BCVA).The secondary efficacy endpoints were improvement in visual field (VF), visual field index (VFI), and mean deviation (MD) and change in retinal nerve fiber layer (RNFL) thickness.

Results: In total,11 mild eye-related AEs occurred in the participants in both groups, and short-term drug treatment returned to normal.The difference was statistically significant in BCVA of the injected eyes in the low-dose group between 12 months after treatment and at baseline.The differences in BCVA of the uninjected eyes in the high-dose group between baseline and 3 months or 6 months after treatment were statistically significant.At 12 months after treatment, the rate of improvement in BCVA for the injected eyes in the low-dose groups was 66.7% (4/6),while BCVA for the uninjected eyes in the high-dose groups was 50.0% (3/6),and patients in both groups had binocular VF (VFI, MD) and RNFL thicknesses that did not significantly differ from baseline.

Conclusion: Preliminary clinical evidence shows that rAAV2-ND1 ophthalmic injection is a safe and effective treatment for LHON due to ND1 mutation.

Trial registration: Trial registration number: ChiCTR2000041574, Date:12/29/2020.