Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration.
Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration.
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DOI：
10.1038/mt.2009.277
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发表时间：
2010-03
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遗传性视网膜疾病基因治疗的安全性和有效性正在Leber先天性黑蒙（LCA）患者中进行测试，LCA是一种常染色体隐性致盲疾病。三项独立的研究提供了证据，证明在因RPE 65基因突变而患有LCA 2的患者中视网膜下施用编码RPE 65的腺相关病毒（AAV）载体是安全的，并且在某些情况下产生疗效。我们评估了由视网膜下施用AAV 2-hRPE 65 v2产生的长期安全性和功效（对视网膜/视觉功能的总体影响）。在我们试验的低剂量队列中入组的3名LCA 2患者中，在早期时间点观察到的安全性和有效性持续到注射后至少1.5年。观察到对AAV衣壳的中和抗体的瞬时升高，但对RPE 65蛋白没有体液应答。持续的功能改善表明，AAV介导的基因转移到人视网膜不引起免疫反应，导致转导细胞的显着损失。生理效应的持续性支持基因治疗可能影响LCA 2疾病进展的可能性。这些受试者中干预的安全性和视觉和视网膜功能改善的稳定性支持使用AAV介导的基因增强疗法治疗遗传性视网膜疾病。
The safety and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber's congenital amaurosis (LCA), an autosomal recessive blinding disease. Three independent studies have provided evidence that the subretinal administration of adeno-associated viral (AAV) vectors encoding RPE65 in patients affected with LCA2 due to mutations in the RPE65 gene, is safe and, in some cases, results in efficacy. We evaluated the long-term safety and efficacy (global effects on retinal/visual function) resulting from subretinal administration of AAV2-hRPE65v2. Both the safety and the efficacy noted at early timepoints persist through at least 1.5 years after injection in the three LCA2 patients enrolled in the low dose cohort of our trial. A transient rise in neutralizing antibodies to AAV capsid was observed but there was no humoral response to RPE65 protein. The persistence of functional amelioration suggests that AAV-mediated gene transfer to the human retina does not elicit immunological responses which cause significant loss of transduced cells. The persistence of physiologic effect supports the possibility that gene therapy may influence LCA2 disease progression. The safety of the intervention and the stability of the improvement in visual and retinal function in these subjects support the use of AAV-mediated gene augmentation therapy for treatment of inherited retinal diseases.
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影响因子：
4.2
作者：
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通讯作者：
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影响因子：
12.4
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