Safety and efficacy of gene transfer for Leber's congenital amaurosis

Albert M Maguire; Francesca Simonelli; Eric A Pierce; Edward N Pugh Jr; Federico Mingozzi; Jeannette Bennicelli; Sandro Banfi; Kathleen A Marshall; Francesco Testa; Enrico M Surace; Settimio Rossi; Arkady Lyubarsky; Valder R Arruda; Barbara Konkle; Edwin Stone; Junwei Sun; Jonathan Jacobs; Lou Dell'Osso; Richard Hertle; Jian-xing Ma; T Michael Redmond; Xiaosong Zhu; Bernd Hauck; Olga Zelenaia; Kenneth S Shindler; Maureen G Maguire; J Fraser Wright; Nicholas J Volpe; Jennifer Wellman McDonnell; Alberto Auricchio; Katherine A High; Jean Bennett

doi:10.1056/NEJMoa0802315

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Safety and efficacy of gene transfer for Leber's congenital amaurosis

Journal article

Open access

Peer reviewed

Safety and efficacy of gene transfer for Leber's congenital amaurosis

Albert M Maguire, Francesca Simonelli, Eric A Pierce, Edward N Pugh Jr, Federico Mingozzi, Jeannette Bennicelli, Sandro Banfi, Kathleen A Marshall, Francesco Testa, Enrico M Surace, …

The New England journal of medicine, Vol.358(21), pp.2240-2248

05/22/2008

DOI: 10.1056/NEJMoa0802315

PMCID: PMC2829748

PMID: 18441370

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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.

Mutation

Dependovirus - genetics

Gene Transfer Techniques

Genetic Therapy

Promoter Regions, Genetic

Retinal Degeneration - genetics

Humans

Blindness - pathology

Visual Acuity

Blindness - genetics

Carrier Proteins - genetics

Injections

Reflex, Pupillary

Retinal Degeneration - therapy

Adult

Blindness - congenital

Blindness - therapy

Eye Proteins - genetics

Retinal Degeneration - congenital

Genetic Vectors

Retinal Degeneration - pathology

Retina - pathology

cis-trans-Isomerases

DNA, Complementary

Details

Title: Subtitle: Safety and efficacy of gene transfer for Leber's congenital amaurosis
Creators: Albert M Maguire - Scheie Eye Institute, University of Pennsylvania, USA
Francesca Simonelli
Eric A Pierce
Edward N Pugh Jr
Federico Mingozzi
Jeannette Bennicelli
Sandro Banfi
Kathleen A Marshall
Francesco Testa
Enrico M Surace
Settimio Rossi
Arkady Lyubarsky
Valder R Arruda
Barbara Konkle
Edwin Stone
Junwei Sun - Children's Hospital of Philadelphia
Jonathan Jacobs
Lou Dell'Osso
Richard Hertle
Jian-xing Ma - University of Oklahoma Medical Center
T Michael Redmond
Xiaosong Zhu
Bernd Hauck
Olga Zelenaia
Kenneth S Shindler
Maureen G Maguire
J Fraser Wright
Nicholas J Volpe
Jennifer Wellman McDonnell
Alberto Auricchio
Katherine A High
Jean Bennett
Resource Type: Journal article
Publication Details: The New England journal of medicine, Vol.358(21), pp.2240-2248
DOI: 10.1056/NEJMoa0802315
PMID: 18441370
PMCID: PMC2829748
NLM abbreviation: N Engl J Med
ISSN: 1533-4406
eISSN: 1533-4406
Publisher: United States
Grant note: EY-10820 / NEI NIH HHS Howard Hughes Medical Institute UL1 RR024134 / NCRR NIH HHS R01 EY010820-11 / NEI NIH HHS R01 EY010820-12 / NEI NIH HHS R01 EY010820-13 / NEI NIH HHS GGP07180 / Telethon R01 EY010820 / NEI NIH HHS TGM06B01 / Telethon
Language: English
Date published: 05/22/2008
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980280702771

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