title: Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year.
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.
authors: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. cideciya@mail.med.upenn.edu
authors: Artur V
authors: AV
authors: Cideciyan
authors: William W
authors: WW
authors: Hauswirth
authors: Tomas S
authors: TS
authors: Aleman
authors: Shalesh
authors: S
authors: Kaushal
authors: Sharon B
authors: SB
authors: Schwartz
authors: Sanford L
authors: SL
authors: Boye
authors: Elizabeth A M
authors: EA
authors: Windsor
authors: Thomas J
authors: TJ
authors: Conlon
authors: Alexander
authors: A
authors: Sumaroka
authors: Ji-Jing
authors: JJ
authors: Pang
authors: Alejandro J
authors: AJ
authors: Roman
authors: Barry J
authors: BJ
authors: Byrne
authors: Samuel G
authors: SG
authors: Jacobson
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics / Q000627:therapeutic use*; D000229:Dependovirus / Q000235:genetics* / Q000276:immunology; D005136:Eye Proteins / Q000235:genetics / Q000627:therapeutic use*; D005500:Follow-Up Studies; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000628:therapy*; D012160:Retina / Q000473:pathology / Q000821:virology*; D016896:Treatment Outcome; D014785:Vision, Ocular; D014792:Visual Acuity; D055815:Young Adult; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D000914:Antibodies, Viral; D002352:Carrier Proteins; D005136:Eye Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase