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Case Report

Three Cases of Leber’s Hereditary Optic Neuropathy with Rapid Increase in Visual Acuity After Gene Therapy

Author(s): Yong Zhang, Jia-jia Yuan, Hong-li Liu, Zhen Tian, Si-wei Liu and Bin Li*

Volume 19, Issue 2, 2019

Page: [134 - 138] Pages: 5

DOI: 10.2174/1566523219666190618094505

open access plus

Abstract

Background: During the first few trials of gene therapy for Leber’s hereditary optic neuropathy performed by our group, the visual acuity of the patients increased gradually over several months, or even years. However, in the current round of gene therapy for Leber’s hereditary optic neuropathy, we noted that the visual acuity of three patients increased rapidly, within a few days after treatment.

Case presentation: Three patients who were diagnosed with mitochondrial gene 11778 mutation (associated with a G-to-A transition at Mt-11778 in the ND4 subunit gene of complex I of mitochondrial DNA that changes an arginine to histidine at amino acid 340) by genetic diagnosis were followed up three times before gene therapy, which lasted for 1 year, without spontaneous improvement of vision. Visual acuity in one or both eyes of each of the three patients increased rapidly after the initial gene therapy treatment.

Conclusion: We suspect that in some patients with Leber’s hereditary optic neuropathy, a portion of the retinal ganglion cells might remain in a “dormant” state for a certain period of time; these may be activated, within an optimal timeframe, during gene therapy for Leber’s hereditary optic neuropathy.

Keywords: Leber's hereditary optic neuropathy, gene therapy, dormant, time window, visual acuity, retinal ganglion cells.

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Graphical Abstract

[1]
Y-Wai-Man P. Turnbull DM. Chinnery PF. Leber hereditary optic neuropathy. J Med Genet 2002; 39: 162-9.
[http://dx.doi.org/10.1136/jmg.39.3.162]
[2]
Peragallo JH, Newman NJ. Is there treatment for Leber hereditary optic neuropathy? Curr Opin Ophthalmol 2015; 26(6): 450-7.
[http://dx.doi.org/10.1097/ICU.0000000000000212] [PMID: 26448041]
[3]
Pilz YL, Bass SJ, Sherman J. A review of mitochondrial optic neuropathies: from inherited to acquired forms. J Optom 2017; 10(4): 205-14.
[http://dx.doi.org/10.1016/j.optom.2016.09.003] [PMID: 28040497]
[4]
Wan X, Pei H, Zhao MJ, et al. Efficacy and safety of rAAV2-ND4 treatment for Leber’s hereditary optic neuropathy. Sci Rep 2016; 6: 21587.
[http://dx.doi.org/10.1038/srep21587] [PMID: 26892229]
[5]
Guy J, Feuer WJ, Davis JL, et al. Gene therapy for Leber hereditary optic neuropathy: Low- and medium-dose visual results. Ophthalmology 2017; 124(11): 1621-34.
[http://dx.doi.org/10.1016/j.ophtha.2017.05.016] [PMID: 28647203]
[6]
Yang S, Ma SQ, Wan X, et al. Long-term outcomes of gene therapy for the treatment of Leber’s hereditary optic neuropathy. EBioMedicine 2016; 10: 258-68.
[http://dx.doi.org/10.1016/j.ebiom.2016.07.002] [PMID: 27426279]
[7]
Brandt U. Energy converting NADH: Quinone oxidoreductase (complex I). Annu Rev Biochem 2006; 75: 69-92.
[http://dx.doi.org/10.1146/annurev.biochem.75.103004.142539] [PMID: 16756485]
[8]
Bi R, Zhang AM, Yu D, Chen D, Yao YG. Screening the three LHON primary mutations in the general Chinese population by using an optimized multiplex allele-specific PCR. Clin Chim Acta 2010; 411(21-22): 1671-4.
[http://dx.doi.org/10.1016/j.cca.2010.06.026] [PMID: 20599858]
[9]
Yang S, He H, Zhu Y, et al. Chemical and material communication between the optic nerves in rats. Clin Exp Ophthalmol 2015; 43(8): 742-8.
[http://dx.doi.org/10.1111/ceo.12547] [PMID: 25950380]
[10]
Luo X, Salgueiro Y, Beckerman SR, Lemmon VP, Tsoulfas P, Park KK. Three-dimensional evaluation of retinal ganglion cell axon regeneration and pathfinding in whole mouse tissue after injury. Exp Neurol 2013; 247: 653-62.
[http://dx.doi.org/10.1016/j.expneurol.2013.03.001] [PMID: 23510761]
[11]
Cen LP, Ng TK, Liang JJ, et al. Human periodontal ligament-derived stem cells promote retinal ganglion cell survival and axon regeneration after optic nerve injury. Stem Cells 2018; 36(6): 844-55.
[http://dx.doi.org/10.1002/stem.2812] [PMID: 29476565]

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