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

被引：1644

作者：

Maguire, Albert M. ^{[1
,2
,3
]}

Simonelli, Francesca ^{[4
,5
]}

Pierce, Eric A. ^{[1
,3
]}

Pugh, Edward N., Jr. ^{[1
]}

Mingozzi, Federico ^{[2
]}

Bennicelli, Jeannette ^{[1
,3
]}

Banfi, Sandro ^{[5
]}

Marshall, Kathleen A. ^{[2
]}

Testa, Francesco ^{[4
]}

Surace, Enrico M. ^{[5
,12
]}

Rossi, Settimio ^{[4
]}

Lyubarsky, Arkady ^{[1
,3
]}

Arruda, Valder R. ^{[2
,3
]}

Konkle, Barbara ^{[3
]}

Stone, Edwin ^{[7
]}

Sun, Junwei ^{[2
]}

Jacobs, Jonathan ^{[8
]}

Dell'Osso, Lou ^{[8
]}

Hertle, Richard ^{[9
]}

Ma, Jian-xing ^{[10
]}

Redmond, T. Michael ^{[11
]}

Zhu, Xiaosong ^{[2
]}

Hauck, Bernd ^{[2
]}

Zelenaia, Olga ^{[2
]}

Shindler, Kenneth S. ^{[1
,3
]}

Maguire, Maureen G. ^{[1
,3
]}

Wright, J. Fraser ^{[2
,3
]}

Volpe, Nicholas J. ^{[1
,3
]}

McDonnell, Jennifer Wellman ^{[2
]}

Auricchio, Alberto ^{[5
,6
]}

High, Katherine A. ^{[2
,3
,12
]}

Bennett, Jean ^{[1
,2
]}

机构：

[1] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA

[2] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[4] Univ Naples 2, Naples, Italy

[5] Telethon Inst Genet & Med, Naples, Italy

[6] Univ Naples Federico 2, Naples, Italy

[7] Univ Iowa, Carver Ctr, Coll Med, Iowa City, IA USA

[8] Vet Affairs Med Ctr, Cleveland, OH USA

[9] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA

[10] Univ Oklahoma, Oklahoma City, OK USA

[11] NEI, Bethesda, MD 20892 USA

[12] Howard Hughes Med Inst, Coconut Grove, FL 33133 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2008年 / 358卷 / 21期

关键词：

D O I：

10.1056/NEJMoa0802315

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.hPPE65v2. 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.

引用

页码：2240 / 2248

页数：9

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