Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis.
Maguire AM,
Simonelli F,
Pierce EA,
Pugh EN Jr,
Mingozzi F,
Bennicelli J,
Banfi S,
Marshall KA,
Testa F,
Surace EM,
Rossi S,
Lyubarsky A,
Arruda VR,
Konkle B,
Stone E,
Sun J,
Jacobs J,
Dell'osso L,
Hertle R,
Ma JX,
Redmond TM,
Zhu X,
Hauck B,
Zelenaia O,
Shindler KS,
Maguire MG,
Wright JF,
Volpe NJ,
McDonnell JW,
Auricchio A,
High KA,
Bennett J.
From the Scheie Eye Institute, University of Pennsylvania (A.M.M., E.A.P., E.N.P., J. Bennicelli, A.L., K.S.S., M.G.M., N.J.V., J. Bennett), Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia (A.M.M., F.M., K.A.M., V.R.A., J.S., X.Z., B.H., O.Z., J.F.W., J.W.M., K.A.H., J. Bennett), and the University of Pennsylvania School of Medicine (A.M.M., E.A.P., J. Bennicelli, A.L., V.R.A., B.K., K.S.S., M.G.M., J.F.W., N.J.V., K.A.H.) — all in Philadelphia; Seconda Universita degli Studi di Napoli (F.S., F.T., S.R.), Telethon Institute of Genetics and Medicine (F.S., S.B., E.M.S., A.A.), and Federico II University (A.A.) — all in Naples; the University of Iowa Carver Center, College of Medicine, Iowa City (E.S.); Veterans Affairs Medical Center, Cleveland (J.J., L.D.); Children's Hospital of Pittsburgh, Pittsburgh (R.H.); the University of Oklahoma, Oklahoma City (J.M.); the National Eye Institute, Bethesda, MD (T.M.R.); and the Howard Hughes Medical Institute (K.A.H., E.S.). Drs. Maguire, Simonelli, Auricchio, High, and Bennett contributed equally to this article.This article (10.1056/NEJMoa0802315) was published at www.nejm.org on April 27, 2008. It will appear in the May 22 issue of the Journal.
Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA. Copyright 2008 Massachusetts Medical Society.
PMID: 18441370 [PubMed - as supplied by publisher]