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Eyal Banin, Alexey Obolensky, Yitzhak Hemo, Devora Marks-Ohana, Malka Sela, Esther Yamin, William Hauswirth, Samuel Jacobson, Dror Sharon; Phase I Gene Therapy Trial in Israeli Patients with Leber Congenital Amaurosis Caused by a Founder RPE65 Mutation: Safety and Efficacy Update with Up to Two Years of Follow-up. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2709.
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© ARVO (1962-2015); The Authors (2016-present)
Gene therapy of human patients with Leber congenital amaurosis (LCA) due to mutations in the RPE65 gene became a reality following demonstration of safety and efficacy in RPE65-mutant dog and mouse models. Our phase I clinical gene therapy trial in Israeli patients, launched in February 2010, was the fourth of its kind worldwide (NCT00821340). The purpose of this report is to describe the results in the first three patients treated, with up to two years of follow-up.
Gene therapy was performed in three LCA patients (ages 21-29 years) who harbor a homozygous splicing mutation (c.95-2A>T; IVS2-2A>T) in the RPE65 gene. Following vitrectomy, subretinal injection of an AAV2-hRPE65 viral vector carrying the normal human RPE65 gene was carried out in one or two sites, avoiding the foveal area. Ocular and systemic safety parameters were monitored closely, including resolution of the subretinal blebs, possible viral spread and immune response to the vector. Visual function and structure were evaluated repeatedly as per protocol by clinical eye exams, computerized light- and dark-adapted perimetry, Goldmann perimetry and non-invasive color, infrared, OCT and autofluorescence imaging.
Two years of follow-up data are available for the first two patients, and 18 months for the third. No toxicity or complications were observed to date in any of the patients. Post-operative data indicates stable visual acuity and increased sensitivity to light in the treated regions in all patients, to varying degrees. In the first patient, up to 100-fold increases persisted through the two year exam, and interestingly, he began to use these extra-foveal areas as his preferred locus for fixation. The third patient also reports and objectively shows significant functional improvement. The treatment effect in the second patient was slow to occur and is less pronounced.
Magnitude of the treatment effect varies between patients, but previous studies by others as well as the present study attest to the safety and efficacy of gene therapy for treatment of RPE65 LCA.
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