title: Safety and efficacy of gene transfer for Leber's congenital amaurosis.
abstract: 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 [ClinicalTrials.gov]). 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.
authors.affiliation: Scheie Eye Institute, University of Pennsylvania, USA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Maguire
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.forename: Eric A
authors.initials: EA
authors.lastname: Pierce
authors.forename: Edward N
authors.initials: EN
authors.lastname: Pugh
authors.forename: Federico
authors.initials: F
authors.lastname: Mingozzi
authors.forename: Jeannette
authors.initials: J
authors.lastname: Bennicelli
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Marshall
authors.forename: Francesco
authors.initials: F
authors.lastname: Testa
authors.forename: Enrico M
authors.initials: EM
authors.lastname: Surace
authors.forename: Settimio
authors.initials: S
authors.lastname: Rossi
authors.forename: Arkady
authors.initials: A
authors.lastname: Lyubarsky
authors.forename: Valder R
authors.initials: VR
authors.lastname: Arruda
authors.forename: Barbara
authors.initials: B
authors.lastname: Konkle
authors.forename: Edwin
authors.initials: E
authors.lastname: Stone
authors.forename: Junwei
authors.initials: J
authors.lastname: Sun
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jacobs
authors.forename: Lou
authors.initials: L
authors.lastname: Dell'Osso
authors.forename: Richard
authors.initials: R
authors.lastname: Hertle
authors.forename: Jian-xing
authors.initials: JX
authors.lastname: Ma
authors.forename: T Michael
authors.initials: TM
authors.lastname: Redmond
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Zhu
authors.forename: Bernd
authors.initials: B
authors.lastname: Hauck
authors.forename: Olga
authors.initials: O
authors.lastname: Zelenaia
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Shindler
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Maguire
authors.forename: J Fraser
authors.initials: JF
authors.lastname: Wright
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Volpe
authors.forename: Jennifer Wellman
authors.initials: JW
authors.lastname: McDonnell
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.forename: Katherine A
authors.initials: KA
authors.lastname: High
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
mesh_terms: D000328:Adult; D001766:Blindness / Q000151:congenital / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002352:Carrier Proteins / Q000235:genetics*; D018076:DNA, Complementary; D000229:Dependovirus / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007267:Injections; D009154:Mutation; D011401:Promoter Regions, Genetic; D012025:Reflex, Pupillary; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000151:congenital / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014792:Visual Acuity; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D005136:Eye Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase