PHASE I TRIAL OF OCULAR SUBRETINAL INJECTION OF A RAAV2-CB - HRPE65

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 重组腺相关病毒血清2型rAAV2载体已被改造为携带人RPE65 hRPE65基因。这种载体已经被证明可以在动物模型中恢复视力，类似于人类RPE65相关的Leber先天性黑色素瘤LCA，一种导致严重视力丧失的不可治愈的视网膜退化。这项拟议的研究是一项开放标签的I期临床试验，即视网膜下rAAV2-CBSB-hRPE65给与RPE65相关视网膜疾病的患者。这项试验将包括两个队列，每个队列三个受试者。这两个队列将接受相同剂量的rAAV2-CBSB-hRPE65。第一组将由18岁及以上的个人组成，第二组将由8岁至17岁的个人组成。只有在确认rAAV2-CBSB-hRPE65在较年长的参与者组中使用的安全性后，才会开始注册第二组。这项试验将使人们更好地了解基因转移治疗RPE65相关视网膜疾病的安全性和潜在价值，并将对适用于此类干预的其他形式的视网膜退行性疾病产生影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A recombinant adeno-associated virus serotype 2 rAAV2 vector has been altered to carry the human RPE65 hRPE65 gene. This vector has been shown to restore vision in animal models that resemble human RPE65-associated Leber congenital amaurosis LCA, an incurable retinal degeneration that causes severe vision loss. The proposed study is an open label, Phase I clinical trial of subretinal rAAV2-CBSB-hRPE65 administration to individuals with RPE65-associated retinal disease. Two cohorts of three subjects each will be included in this trial. Both cohorts will receive the same dose of rAAV2-CBSB-hRPE65 . Cohort 1 will consist of individuals 18 years of age and older and Cohort 2 will consist of individuals between the ages of 8 and 17. Enrollment in Cohort 2 will begin only after confirming the safety of rAAV2-CBSB-hRPE65 administration in the older group of participants. This trial will lead to a greater understanding of the safety and thereby potential value of gene transfer in RPE65-associated retinal disease and will have implications for other forms of retinal degenerative disease amenable to this type of intervention.