Human RPE65 Gene Therapy for Leber Congenital Amaurosis: Persistence of Early Visual Improvements and Safety at 1 Year
Human RPE65 Gene Therapy for Leber Congenital Amaurosis: Persistence of Early Visual Improvements and Safety at 1 Year
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DOI：
10.1089/hum.2009.086
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发表时间：
2009-09-01
影响因子：
4.2
通讯作者：
Jacobson, Samuel G.
中科院分区：
文献类型：
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作者：
Cideciyan, Artur V.;Hauswirth, William W.;Jacobson, Samuel G.
用raav2载体对RPE65型儿童失明Leber先天性黑朦进行人类基因治疗。在三个独立小组同时进行的研究中，该手术被认为是安全的，并且有证据表明在短期内视力恢复。在治疗后12个月，我们的年轻成人受试者保持健康，没有与病媒相关的严重不良事件。鉴定对AAV血清2型衣壳反应的免疫学检测结果与基线测量结果没有变化。研究眼和对照眼的临床眼科检查结果，包括视力和视网膜中央结构，在体内显微镜下，与3个月时的结果没有差异。我们在3个月时报告的视觉灵敏度的显著改善在12个月时没有改变。3 ~ 12个月视敏的视杆和视锥成分的视网膜范围和大小也相同。用rAAV2-RPE65载体进行人视网膜基因转移的安全性和有效性可延长至治疗后至少1年。
Human gene therapy with rAAV2-vector was performed for the RPE65 form of childhood blindness called Leber congenital amaurosis. In three contemporaneous studies by independent groups, the procedure was deemed safe and there was evidence of visual gain in the short term. At 12 months after treatment, our young adult subjects remained healthy and without vector-related serious adverse events. Results of immunological assays to identify reaction to AAV serotype 2 capsid were unchanged from baseline measurements. Results of clinical eye examinations of study and control eyes, including visual acuities and central retinal structure by in vivo microscopy, were not different from those at the 3-month time point. The remarkable improvements in visual sensitivity we reported by 3 months were unchanged at 12 months. The retinal extent and magnitude of rod and cone components of the visual sensitivity between 3 and 12 months were also the same. The safety and efficacy of human retinal gene transfer with rAAV2-RPE65 vector extends to at least 1 year posttreatment.