Efficacy evaluation of intravitreal injection of rAAV2-ND4 gene for Leber hereditary optic neuropathy

Authors: Li Xin,  Tian Zhen,  Chen Zhang,  Li Bin,  Zhang Yong
DOI: 10.3760/cma.j.cn115989-20210330-00218
Published 2021-08-10
Cite asChin J Exp Ophthalmol, 2021, 39(8): 724-728.

Abstract

Objective

To evaluate the safety and clinical effect of gene therapy for Leber hereditary optic neuropathy (LHON).

Methods

A multi-center prospective non-randomized controlled trial was conducted.Eighty eyes of 40 LHON patients with mitochondrial DNA 11778 mutation were enrolled in Taihe Hospital from December 2017 to February 2018.Intravitreal injection of recombinant adeno associated virus 2-NADH dehydrogenase 4 (rAAV2-ND4) was carried out in the unilateral eye with worse visual acuity or the right eye (if the visual acuity of both eyes was equal) of each subject as the treated group and the fellow eyes as the untreated group.The best corrected visual acuity (BCVA) was detected using a standard logarithmic chart and intraocular pressure (IOP) was measured with a non-contact tonometer before treatment and 1, 3, 6, 12 months after treatment.The manifestations of the ocular anterior segment and fundus were examined by slit lamp microscopy and color photography.The changes of visual acuity and IOP before and after gene therapy were compared, and complications were evaluated between the treated group and the untreated group.The effective rate defined as visual acuity improved ≥0.3 LogMAR at the end of follow-up was assessed.This study adhered to the Declaration of Helsinki and the study protocol was approved by an Ethics Committee of Taihe Hospital (No.201807). Written informed consent was obtained from each subject prior to any medical examination and treatment.

Results

The visual acuity improved 6 eyes in the treated group and 4 eyes in the untreated group, and 13 patients showed bilateral improvement.The visual acuity improvement ≥0.3 LogMAR in 23 patients with the effective rate 57.5%.The BCVA was (1.51±0.62) LogMAR and (1.62±0.58) LogMAR at the end of following-up in the untreated group and treated group, respectively, which were significantly higher than (1.75±0.46) LogMAR and (1.83±0.47) LogMAR before treatment (both at P<0.01), and no significant difference was found in BCVA between the two groups (Fgroup=0.084, P=0.772). There was no significant difference in IOP between the two groups before and after treatment (Fgroup=0.557, P=0.575; Ftime=2.314, P=0.106). No serious complications were found in all subjects during following-up.

Conclusions

rAAV2-ND4 gene therapy is safe and effective for LHON, and binocular vision can be improved by monocular intravitreal injection of rAAV2-ND4 gene.

Key words:

Leber hereditary optic neuropathy; Recombinant adeno associated virus 2-NADH dehydrogenase 4; Gene therapy; Visual acuity; Intravitreal injection

Contributor Information

Li Xin

Department of Ophthalmology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China

Tian Zhen

Department of Ophthalmology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China

Chen Zhang

Department of Ophthalmology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China

Li Bin

Department of Ophthalmology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China

Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Wuhan Neurophth Biological Technology Limited Company, Wuhan 420200, China

Zhang Yong

Department of Ophthalmology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China

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Updated: August 10, 2021 — 8:47 am