Safety Study of an Adeno-associated Virus Vector for Gene Therapy of Leber's Hereditary Optic Neuropathy

Summary

The study is a dose-escalation study, phase 1. The objective of this proposed clinical trial is to evaluate the safety of mitochondrially targeted ND4 gene therapy with the adeno-associated viral vector in appropriate LHON patients.

Timeline

Start

2014-07-14

Primary completion

2023-03-31

Completion

2025-03-31

Publications

• Results Feuer WJ, Schiffman JC, Davis JL, Porciatti V, Gonzalez P, Koilkonda RD, Yuan H, Lalwani A, Lam BL, Guy J. Gene Therapy for Leber Hereditary Optic Neuropathy: Initial Results. Ophthalmology. 2016 Mar;123(3):558-70. doi: 10.1016/j.ophtha.2015.10.025. Epub 2015 Nov 19.
• Results Guy J, Feuer WJ, Davis JL, Porciatti V, Gonzalez PJ, Koilkonda RD, Yuan H, Hauswirth WW, Lam BL. Gene Therapy for Leber Hereditary Optic Neuropathy: Low- and Medium-Dose Visual Results. Ophthalmology. 2017 Nov;124(11):1621-1634. doi: 10.1016/j.ophtha.2017.05.016. Epub 2017 Jun 21.
• Results Lam BL, Feuer WJ, Davis JL, Porciatti V, Yu H, Levy RB, Vanner E, Guy J. Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups. Am J Ophthalmol. 2022 Sep;241:262-271. doi: 10.1016/j.ajo.2022.02.023. Epub 2022 Mar 7.
• Results Lam BL, Feuer WJ, Porciatti V, Davis JL, Zheng DD, Vanner EA, Savatovsky EJ, Alba DE, Guy J. Leber Hereditary Optic Neuropathy Gene Therapy: Longitudinal Relationships Among Visual Function and Anatomical Measures. Am J Ophthalmol. 2024 Jan;257:113-128. doi: 10.1016/j.ajo.2023.09.005. Epub 2023 Sep 15.
• Results Porciatti V, Alba DE, Feuer WJ, Davis J, Guy J, Lam BL. The Relationship Between Stage of Leber's Hereditary Optic Neuropathy and Pattern Electroretinogram Latency. Transl Vis Sci Technol. 2022 Mar 2;11(3):31. doi: 10.1167/tvst.11.3.31.
• Results Lam BL. Leber hereditary optic neuropathy gene therapy. Curr Opin Ophthalmol. 2024 May 1;35(3):244-251. doi: 10.1097/ICU.0000000000001028. Epub 2023 Dec 20.
• Results Lam BL, Burke SP, Wang MX, Nadayil GA, Rosa PR, Gregori G, Feuer WJ, Cuprill-Nilson S, Vandenbroucke R, Zhang X, Guy J. Macular Retinal Sublayer Thicknesses in G11778A Leber Hereditary Optic Neuropathy. Ophthalmic Surg Lasers Imaging Retina. 2016 Sep 1;47(9):802-10. doi: 10.3928/23258160-20160901-02.
• Results Koilkonda R, Yu H, Talla V, Porciatti V, Feuer WJ, Hauswirth WW, Chiodo V, Erger KE, Boye SL, Lewin AS, Conlon TJ, Renner L, Neuringer M, Detrisac C, Guy J. LHON gene therapy vector prevents visual loss and optic neuropathy induced by G11778A mutant mitochondrial DNA: biodistribution and toxicology profile. Invest Ophthalmol Vis Sci. 2014 Oct 23;55(12):7739-53. doi: 10.1167/iovs.14-15388.
• Results Guy J, Feuer WJ, Porciatti V, Schiffman J, Abukhalil F, Vandenbroucke R, Rosa PR, Lam BL. Retinal ganglion cell dysfunction in asymptomatic G11778A: Leber hereditary optic neuropathy. Invest Ophthalmol Vis Sci. 2014 Feb 10;55(2):841-8. doi: 10.1167/iovs.13-13365.
• Results Koilkonda RD, Yu H, Chou TH, Feuer WJ, Ruggeri M, Porciatti V, Tse D, Hauswirth WW, Chiodo V, Boye SL, Lewin AS, Neuringer M, Renner L, Guy J. Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial. JAMA Ophthalmol. 2014 Apr 1;132(4):409-20. doi: 10.1001/jamaophthalmol.2013.7630.
• Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.

Drugs

Indications