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Published Online: 3 August 2009

Human RPE65 Gene Therapy for Leber Congenital Amaurosis: Persistence of Early Visual Improvements and Safety at 1 Year

Publication: Human Gene Therapy
Volume 20, Issue Number 9

Abstract

Human gene therapy with rAAV2-vector was performed for the RPE65 form of childhood blindness called Leber congenital amaurosis. In three contemporaneous studies by independent groups, the procedure was deemed safe and there was evidence of visual gain in the short term. At 12 months after treatment, our young adult subjects remained healthy and without vector-related serious adverse events. Results of immunological assays to identify reaction to AAV serotype 2 capsid were unchanged from baseline measurements. Results of clinical eye examinations of study and control eyes, including visual acuities and central retinal structure by in vivo microscopy, were not different from those at the 3-month time point. The remarkable improvements in visual sensitivity we reported by 3 months were unchanged at 12 months. The retinal extent and magnitude of rod and cone components of the visual sensitivity between 3 and 12 months were also the same. The safety and efficacy of human retinal gene transfer with rAAV2-RPE65 vector extends to at least 1 year posttreatment.

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Information

Published In

cover image Human Gene Therapy
Human Gene Therapy
Volume 20Issue Number 9September 2009
Pages: 999 - 1004
PubMed: 19583479

History

Published in print: September 2009
Published online: 3 August 2009
Published ahead of production: 7 July 2009
Accepted: 3 July 2009
Received: 18 May 2009

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Authors

Affiliations

Artur V. Cideciyan
Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104.
William W. Hauswirth
Department of Ophthalmology, University of Florida, Gainesville, FL 32610.
Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610.
Tomas S. Aleman
Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104.
Shalesh Kaushal
Department of Ophthalmology, University of Florida, Gainesville, FL 32610.
Sharon B. Schwartz
Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104.
Sanford L. Boye
Department of Ophthalmology, University of Florida, Gainesville, FL 32610.
Elizabeth A.M. Windsor
Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104.
Thomas J. Conlon
Department of Ophthalmology, University of Florida, Gainesville, FL 32610.
Alexander Sumaroka
Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104.
Ji-jing Pang
Department of Ophthalmology, University of Florida, Gainesville, FL 32610.
Alejandro J. Roman
Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104.
Barry J. Byrne
Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610.
Samuel G. Jacobson
Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104.

Notes

Address correspondence to:
Dr. Artur V. Cideciyan
Scheie Eye Institute
University of Pennsylvania
Philadelphia, PA 19104
E-mail: [email protected]

Author Disclosure Statement

B.J.B., W.W.H., and the University of Florida have a financial interest in the use of AAV therapies, and own equity in a company (AGTC Inc.) that might, in the future, commercialize some aspects of this work. S.K. is a principal investigator of a clinical trial of AAV-RPE65 to treat LCA sponsored by AGTC. The University of Pennsylvania, University of Florida, and Cornell University hold a patent on the described gene therapy technology (U.S. Patent 20070077228, “Method for Treating or Retarding the Development of Blindness”).

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