Leber遗传性视神经病变的基因治疗进展

doi:10.6040/j.issn.1673-3770.0.2023.074

Abstract

Abstract: Leber hereditary optic neuropathy(LHON)is a maternal hereditary mitochondrial disease which is a common cause of bilateral teenaged blindness. LHON is a complex and multifactorial disease for which more than 50 associated mitochondrial DNA(mtDNA)mutations have been found. Further, about 90% of global Leber hereditary optic neuropathy cases have the mtDNA mutations m.11778G>A, m.3460G>A, or m.14484T>C. As an important method of future medical treatment, gene therapy is becoming a hot spot in current research, and gene therapies targeting mtDNA mutations are among the fastest developing of these therapies. Currently, basic research on gene therapies targeting mtDNA mutations has demonstrated its safety in animal studies. Currently, different teams are initiating clinical phase I/II studies of the safety and efficacy of gene therapy products in patients. Herein, we review the progress of gene therapy for LHON.

Key words: Leber hereditary optic neuropathy, Gene therapy, Mitochondrial disease, Gene mutation

CLC Number:

R774.6

LIU Ruowu, ZHANG Han. Gene therapy for leber hereditary optic neuropathy[J].Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(4): 154-158.

References

[1] Yu-Wai-Man P, Turnbull DM, Chinnery PF. Leber hereditary optic neuropathy[J]. J Med Genet, 2002, 39(3): 162-169. doi:10.1136/jmg.39.3.162
[2] Carelli V, Carbonelli M, de Coo IF, et al. International consensus statement on the clinical and therapeutic management of leber hereditary optic neuropathy[J]. J Neuroophthalmol, 2017, 37(4): 371-381. doi:10.1097/WNO.0000000000000570
[3] Man PYW, Griffiths PG, Brown DT, et al. The epidemiology of leber hereditary optic neuropathy in the north east of England[J]. Am J Hum Genet, 2003, 72(2): 333-339. doi:10.1086/346066
[4] Yu-Wai-Man P, Votruba M, Burté F, et al. A neurodegenerative perspective on mitochondrial optic neuropathies[J]. Acta Neuropathol, 2016, 132(6): 789-806. doi:10.1007/s00401-016-1625-2
[5] Cwerman-Thibault H, Augustin S, Lechauve C, et al. Nuclear expression of mitochondrial ND4 leads to the protein assembling in complex I and prevents optic atrophy and visual loss[J]. Mol Ther Methods Clin Dev, 2015, 2: 15003. doi:10.1038/mtm.2015.3
[6] Lopez Sanchez MIG, Kearns LS, Staffieri SE, et al. Establishing risk of vision loss in Leber hereditary optic neuropathy[J]. Am J Hum Genet, 2021, 108(11): 2159-2170. doi:10.1016/j.ajhg.2021.09.015
[7] Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with leber's hereditary optic neuropathy[J]. Science, 1988, 242(4884): 1427-1430. doi:10.1126/science.3201231
[8] Johns DR, Smith KH, Savino PJ, et al. Leber's hereditary optic neuropathy. Clinical manifestations of the 15257 mutation[J]. Ophthalmology, 1993, 100(7): 981-986. doi:10.1016/s0161-6420(93)31527-7
[9] Meunier I, Lenaers G, Hamel C, et al. Hereditary optic neuropathies: from clinical signs to diagnosis[J]. J Fr Ophtalmol, 2013, 36(10): 886-900. doi:10.1016/j.jfo.2013.05.007
[10] Balducci N, Savini G, Cascavilla ML, et al. Macular nerve fibre and ganglion cell layer changes in acute Leber's hereditary optic neuropathy[J]. Br J Ophthalmol, 2016, 100(9): 1232-1237. doi:10.1136/bjophthalmol-2015-307326
[11] Barboni P, Carbonelli M, Savini G, et al. Natural history of leber's hereditary optic neuropathy: longitudinal analysis of the retinal nerve fiber layer by optical coherence tomography[J]. Ophthalmology, 2010, 117(3): 623-627. doi:10.1016/j.ophtha.2009.07.026
[12] Manjunath V, Bhatti MT. Leber hereditary optic neuropathy and multiple sclerosis: the mitochondrial connection[J]. Can J Ophthalmol, 2015, 50(1): e14-e17. doi:10.1016/j.jcjo.2014.10.018
[13] Yuka W, Masaaki O, Koichi H. Case of Leber's hereditary optic neuropathy with mitochondrial DNA 11778 mutation exhibiting cerebellar ataxia, dilated cardiomyopathy and peripheral neuropathy[J]. Brain Nerve=Shinkei Kenkyu Shinpo, 2009, 61(3): 309-12
[14] Saracchi E, DiFrancesco JC, Brighina L, et al. A case of Leber hereditary optic neuropathy plus dystonia caused by G14459A mitochondrial mutation[J]. Neurol Sci, 2013, 34(3): 407-408. doi:10.1007/s10072-012-1013-1
[15] DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases[J]. N Engl J Med, 2003, 348(26): 2656-2668. doi:10.1056/nejmra022567
[16] Guy J, Qi XP, Pallotti F, et al. Rescue of a mitochondrial deficiency causing Leber hereditary optic neuropathy[J]. Ann Neurol, 2002, 52(5): 534-542. doi:10.1002/ana.10354
[17] Yu H, Mehta A, Wang GF, et al. Next-generation sequencing of mitochondrial targeted AAV transfer of human ND4 in mice[J]. Mol Vis, 2013, 19: 1482-1491. doi:10.1016/j.ydbio.2013.04.016
[18] 丁芝祥, 谭浅. 腺相关病毒载体在眼病基因治疗中的应用及研究进展[J]. 国际眼科杂志, 2009, 9(6): 1125-1127. doi:10.3969/j.issn.1672-5123.2009.06.038 Ding ZX, Tan Q. Progress in gene therapy for eye diseases using adeno-associated virus as a vector[J]. International Journal of Ophthalmology, 2009, 9(6): 1125-1127. doi:10.3969/j.issn.1672-5123.2009.06.038
[19] Guy J, Qi XP, Koilkonda RD, et al. Efficiency and safety of AAV-mediated gene delivery of the human ND4 complex I subunit in the mouse visual system[J]. Invest Ophthalmol Vis Sci, 2009, 50(9): 4205. doi:10.1167/iovs.08-3214
[20] Shi H, Gao J, Pei H, et al. Adeno-associated virus-mediated gene delivery of the human ND4 complex I subunit in rabbit eyes[J]. Clin Exp Ophthalmol, 2012, 40(9): 888-894. doi:10.1111/j.1442-9071.2012.02815.x
[21] Yang S, Ma SQ, Wan X, et al. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy[J]. eBioMedicine, 2016, 10: 258-268. doi:10.1016/j.ebiom.2016.07.002
[22] Yuan JJ, Zhang Y, Liu HL, et al. Seven-year follow-up of gene therapy for leber's hereditary optic neuropathy[J]. Ophthalmology, 2020, 127(8): 1125-1127. doi:10.1016/j.ophtha.2020.02.023
[23] Feuer WJ, Schiffman JC, Davis JL, et al. Gene therapy for leber hereditary optic neuropathy[J]. Ophthalmology, 2016, 123(3): 558-570. doi:10.1016/j.ophtha.2015.10.025
[24] Lam BL, Feuer WJ, Davis JL, et al. Leber hereditary optic neuropathy gene therapy: adverse events and visual acuity results of all patient groups[J]. Am J Ophthalmol, 2022, 241: 262-271. doi:10.1016/j.ajo.2022.02.023
[25] Vignal C, Uretsky S, Fitoussi S, et al. Safety of rAAV2/2-ND4 gene therapy for leber hereditary optic neuropathy[J]. Ophthalmology, 2018, 125(6): 945-947. doi:10.1016/j.ophtha.2017.12.036
[26] Newman Nancy J, Patrick YWM, Valerio C, et al. Efficacy and safety of intravitreal gene therapy for leber hereditary optic neuropathy treated within 6 months of disease onset[J]. Ophthalmology, 2021, 128(5): 649-660. doi:10.1016/j.ophtha.2020.12.012
[27] Yu-Wai-Man P, Newman NJ, Carelli V, et al. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy[J]. Sci Transl Med, 2020, 12(573): eaaz7423. doi:10.1126/scitranslmed.aaz7423
[28] Biousse V, Newman NJ, Yu-Wai-Man P, et al. Long-term follow-up after unilateral intravitreal gene therapy for leber hereditary optic neuropathy: the RESTORE study[J]. J Neuro Ophthalmol, 2020, 41(3): 309-315. doi:10.1097/wno.0000000000001367
[29] Newman NJ, Yu-Wai-Man P, Subramanian, PS, et al. Randomized trial of bilateral gene therapy injection for m. 11778G> A MT-ND4 Leber optic neuropathy[J]. Brain, 2022, 146: 1328-1341. doi: 10.1093/brain/awac421
[30] Carelli V, Newman NJ, Yu-Wai-Man P, et al. Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in patients with leber hereditary optic neuropathy carrying the m. 11778G> A MT-ND4 Mutation[J]. Ophthalmology and Therapy, 2023, 12(1): 401-429.doi: 10.1007/s40123-022-00611-x
[31] Wan X, Pei H, Zhao MJ, et al. Efficacy and safety of rAAV2-ND4 treatment for leber's hereditary optic neuropathy[J]. Sci Rep, 2016, 6: 21587. doi:10.1038/srep21587
[32] Zhang Y, Li X, Yuan JJ, et al. Prognostic factors for visual acuity in patients with Leber's hereditary optic neuropathy after rAAV2-ND4 gene therapy[J]. Clin Exp Ophthalmol, 2019, 47(6): 774-778. doi:10.1111/ceo.13515
[33] Yang S, He H, Zhu Y, et al. Chemical and material communication between the optic nerves in rats[J]. Clin Exp Ophthalmol, 2015, 43(8): 742-748. doi:10.1111/ceo.12547

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