Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis
James W.B. Bainbridge, Ph.D., F.R.C.Ophth., Alexander J. Smith, Ph.D., Susie S. Barker, Ph.D., Scott Robbie, M.R.C.Ophth., Robert Henderson, M.R.C.Ophth., Kamaljit Balaggan, M.R.C.Ophth., Ananth Viswanathan, M.D., F.R.C.Ophth., Graham E. Holder, Ph.D., Andrew Stockman, Ph.D., Nick Tyler, Ph.D., Simon Petersen-Jones, Ph.D., Shomi S. Bhattacharya, Ph.D., Adrian J. Thrasher, Ph.D., M.R.C.P., F.R.C.P., Fred W. Fitzke, Ph.D., Barrie J. Carter, Ph.D., Gary S. Rubin, Ph.D., Anthony T. Moore, F.R.C.Ophth., and Robin R. Ali, Ph.D.
Early-onset, severe retinal dystrophy caused by mutations inthe gene encoding retinal pigment epithelium–specific65-kD protein (RPE65) is associated with poor vision at birthand complete loss of vision in early adulthood. We administeredto three young adult patients subretinal injections of recombinantadeno-associated virus vector 2/2 expressing RPE65 complementaryDNA (cDNA) under the control of a human RPE65 promoter. Therewere no serious adverse events. There was no clinically significantchange in visual acuity or in peripheral visual fields on Goldmannperimetry in any of the three patients. We detected no changein retinal responses on electroretinography. One patient hadsignificant improvement in visual function on microperimetryand on dark-adapted perimetry. This patient also showed improvementin a subjective test of visual mobility. These findings providesupport for further clinical studies of this experimental approachin other patients with mutant RPE65. (ClinicalTrials.gov number,NCT00643747
[ClinicalTrials.gov]
.)
Source Information
From the Institute of Ophthalmology, University College London (J.W.B.B., A.J.S., S.S. Barker, S.R., R.H., K.B., A.V., G.E.H., A.S., S.S. Bhattacharya, F.W.F., G.S.R., A.T.M., R.R.A.); Moorfields Eye Hospital (J.W.B.B., A.V., G.E.H., A.T.M.); the National Institute of Health Research Biomedical Research Centre for Ophthalmology, University College London and Moorfields Eye Hospital (J.W.B.B., G.S.R., A.T.M., R.R.A.); the Department of Civil and Environmental Engineering, University College London (N.T.); and the Institute of Child Health, University College London (A.J.T., R.R.A.) — all in London; Michigan State University, East Lansing (S.P.-J.); and Targeted Genetics Corporation, Seattle (B.J.C.). Drs. Bainbridge and Smith contributed equally to this article. This article (10.1056/NEJMoa0802268) was published at www.nejm.org on April 27, 2008.
Address reprint requests to Dr. Ali at the Institute of Ophthalmology, University College London, Bath St., London EC1V 9EL, United Kingdom, or at r.ali{at}ucl.ac.uk.
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