Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2
Francesco Testa, Albert M Maguire, Settimio Rossi, Eric A Pierce, Paolo Melillo, Kathleen Marshall, Sandro Banfi, Enrico M Surace, Junwei Sun, Carmela Acerra, J Fraser Wright, Jennifer Wellman, Katherine A High, Alberto Auricchio, Jean Bennett, Francesca Simonelli, Francesco Testa, Albert M Maguire, Settimio Rossi, Eric A Pierce, Paolo Melillo, Kathleen Marshall, Sandro Banfi, Enrico M Surace, Junwei Sun, Carmela Acerra, J Fraser Wright, Jennifer Wellman, Katherine A High, Alberto Auricchio, Jean Bennett, Francesca Simonelli
Abstract
Objective: The aim of this study was to show the clinical data of long-term (3-year) follow-up of 5 patients affected by Leber congenital amaurosis type 2 (LCA2) treated with a single unilateral injection of adeno-associated virus AAV2-hRPE65v2.
Design: Clinical trial.
Participants: Five LCA2 patients with RPE65 gene mutations.
Methods: After informed consent and confirmation of trial eligibility criteria, the eye with worse visual function was selected for subretinal delivery of adeno-associated virus (AAV2-hRPE65v2). Subjects were evaluated before and after surgery at designated follow-up visits (1, 2, 3, 14, 30, 60, 90, 180, 270, and 365 days, 1.5 years, and 3 years) by complete ophthalmic examination. Efficacy for each subject was monitored with best-corrected visual acuity, kinetic visual field, nystagmus testing, and pupillary light reflex.
Main outcome measures: Best-corrected visual acuity, kinetic visual field, nystagmus testing, and pupillary light reflex.
Results: The data showed a statistically significant improvement of best-corrected visual acuity between baseline and 3 years after treatment in the treated eye (P<0.001). In all patients, an enlargement of the area of visual field was observed that remained stable until 3 years after injection (average values: baseline, 1058 deg(2) vs. 3 years after treatment, 4630 deg(2)) and a reduction of the nystagmus frequency compared with baseline at the 3-year time point. Furthermore, a statistically significant difference was observed in the pupillary constriction of the treated eye (P<0.05) compared with the untreated eye in 3 patients at 1- and 3-year time points. No patients experienced serious adverse events related to the vector in the 3-year postinjection period.
Conclusions: The long-term follow-up data (3 years) on the 5-patient Italian cohort involved in the LCA2 gene therapy clinical trial clearly showed a stability of improvement in visual and retinal function that had been achieved a few months after treatment. Longitudinal data analysis showed that the maximum improvement was achieved within 6 months after treatment, and the visual improvement was stable up to the last observed time point.
Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.
Conflict of interest statement
Conflict of interest: J.B. and A.M.M. are co-inventors on a patent (2797-11-US) for a method to treat or slow the development of blindness, but both waived any financial interest in this technology in 2002. K.A.H. and J.F.W. are co-inventors on a patent regarding methods of making AAV vectors for clinical studies (U.S. patent 61/299,184, 2010). J.B. and J.F.W. serve on the scientific advisory board for Avalanche Technologies. J.F.W. has consulted for Tacere Therapeutics, Genzyme, Novartis, and Genetix Inc. The other authors declare that they have no competing interests
Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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Source: PubMed