Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy
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Authors
Weleber, Richard G.Pennesi, Mark E.
Wilson, David J.
Kaushal, Shalesh
Erker, Laura R.
Jensen, Lauren
McBride, Maureen T.
Flotte, Terence R.
Humphries, Margaret
Calcedo, Roberto
Hauswirth, William W.
Chulay, Jeffrey D.
Stout, J. Timothy
UMass Chan Affiliations
Department of OphthalmologyDocument Type
Journal ArticlePublication Date
2016-07-01
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PURPOSE: To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations. DESIGN: Nonrandomized, multicenter clinical trial. PARTICIPANTS: Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD). METHODS: Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment. MAIN OUTCOME MEASURES: The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30 degrees visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire. RESULTS: All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area. CONCLUSIONS: Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns.Source
Ophthalmology. 2016 Jul;123(7):1606-20. doi: 10.1016/j.ophtha.2016.03.003. Epub 2016 Apr 19. Link to article on publisher's siteDOI
10.1016/j.ophtha.2016.03.003Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39994PubMed ID
27102010Related Resources
Link to Article in PubMedDistribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.ophtha.2016.03.003
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/4.0/