TY - JOUR
T1 - Safety and efficacy of gene transfer for Leber's congenital amaurosis
AU - Maguire, Albert M.
AU - Simonelli, Francesca
AU - Pierce, Eric A.
AU - Pugh, Edward N.
AU - Mingozzi, Federico
AU - Bennicelli, Jeannette
AU - Banfi, Sandro
AU - Marshall, Kathleen A.
AU - Testa, Francesco
AU - Surace, Enrico M.
AU - Rossi, Settimio
AU - Lyubarsky, Arkady
AU - Arruda, Valder R.
AU - Konkle, Barbara
AU - Stone, Edwin
AU - Sun, Junwei
AU - Jacobs, Jonathan
AU - Dell'Osso, Lou
AU - Hertle, Richard
AU - Ma, Jian Xing
AU - Redmond, T. Michael
AU - Zhu, Xiaosong
AU - Hauck, Bernd
AU - Zelenaia, Olga
AU - Shindler, Kenneth S.
AU - Maguire, Maureen G.
AU - Wright, J. Fraser
AU - Volpe, Nicholas J.
AU - McDonnell, Jennifer Wellman
AU - Auricchio, Alberto
AU - High, Katherine A.
AU - Bennett, Jean
N1 - Funding Information:
Supported by the Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia, the Foundation Fighting Blindness sponsored by the Pediatric Center for Retinal Degenerations, Research to Prevent Blindness, a grant (EY-10820) from the National Institutes of Health, the Macula Vision Foundation, the Paul and Evanina Mackall Foundation Trust, the Scheie Eye Institute, the F.M. Kirby Foundation, grants (TIGEM-P21, to Drs. Auricchio, Surace, and Banfi, and GGP07180, to Dr. Simonelli) from the Italian Telethon Foundation, a grant (UL1-RR-024134) from the National Center for Research Resources, the Rosanne H. Silbermann Foundation, the Associazione Italiana Amaurosi Congenita di Leber, and the Howard Hughes Medical Institute (to Drs. Stone and High).
PY - 2008/5/22
Y1 - 2008/5/22
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJMoa0802315
DO - 10.1056/NEJMoa0802315
M3 - Article
C2 - 18441370
AN - SCOPUS:44249085878
SN - 0028-4793
VL - 358
SP - 2240
EP - 2248
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 21
ER -