Safety and efficacy of gene transfer for Leber's congenital amaurosis
Safety and efficacy of gene transfer for Leber's congenital amaurosis
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DOI：
10.1056/nejmoa0802315
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发表时间：
2008-05-22
影响因子：
158.5
通讯作者：
Bennett, Jean
中科院分区：
文献类型：
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作者：
Maguire, Albert M.;Simonelli, Francesca;Bennett, Jean
Leber氏先天性黑蒙（LCA）是一组在儿童期发病的遗传性致盲性疾病。这种疾病的一种形式LCA2是由视网膜色素上皮特异性65 kDa蛋白基因（RPE 65）突变引起的。我们研究了视网膜下递送携带RPE 65互补DNA（cDNA）的重组腺相关病毒（AAV）（ClinicalTrials.gov编号，NCT 00516477）的安全性。三名患有LCA 2的患者在递送AAV2.hPPE 65v2后具有可接受的局部和全身不良事件特征。每例患者在主观视力测试中的视网膜功能指标均有适度改善。在一名患者中，出现了无症状的黄斑裂孔，尽管该事件被认为是不良事件，但该患者的视网膜功能有所恢复。虽然随访时间很短，视力也没有达到正常，但这项研究为LCA患者的进一步基因治疗研究提供了基础。
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.