Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: Results of a phase I clinical trial
Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: Results of a phase I clinical trial
复制标题
DOI：
10.1089/hum.2006.17.167
复制
发表时间：
2006-02-01
影响因子：
4.2
通讯作者：
Wei, LL
中科院分区：
文献类型：
--
作者：
Campochiaro, PA;Nguyen, QD;Wei, LL
28例晚期新生血管性年龄相关性黄斑变性（AMD）患者接受了E1、部分E3、E4缺失的腺病毒载体表达人色素上皮衍生因子（AdPEDF. 11）的玻璃体内注射。研究的剂量范围为10（6）至10（9.5）个颗粒单位（PU）。没有与AdPEDF.11相关的严重不良事件，也没有剂量限制性毒性。25%的患者出现轻度、短暂的眼内炎症体征，但无严重炎症。6例患者出现眼内压升高，局部用药易于控制。所有腺病毒培养均为阴性。在注射后3个月和6个月，分别有55%和50%的10（6）-10（7.5）PU治疗患者和94%和71%的10（8）-10（9.5）PU治疗患者的病变尺寸较基线无变化或改善。低剂量组6个月和12个月时病灶大小的中位增加为0.5和1.0个椎间盘面积，而高剂量组为0和0个椎间盘面积。这些数据表明，在单次玻璃体内注射剂量大于108 PU的AdPEDF后，抗血管生成活性可能持续数月。这项研究提供的证据表明，腺病毒载体介导的眼部基因转移是一种可行的方法，用于治疗眼部疾病，并应进行进一步的研究调查的疗效AdPEDF。
Twenty-eight patients with advanced neovascular age-related macular degeneration (AMD) were given a single intravitreous injection of an E1-, partial E3-, E4-deleted adenoviral vector expressing human pigment epithelium-derived factor (AdPEDF.11). Doses ranging from 10(6) to 10(9.5) particle units (PU) were investigated. There were no serious adverse events related to AdPEDF.11 and no dose-limiting toxicities. Signs of mild, transient intraocular inflammation occurred in 25% of patients, but there was no severe inflammation. Six patients experienced increased intraocular pressure that was easily controlled by topical medication. All adenoviral cultures were negative. At 3 and 6 months after injection, 55 and 50%, respectively, of patients treated with 10(6)-10(7.5) PU and 94 and 71% of patients treated with 10(8)-10(9.5) PU had no change or improvement in lesion size from baseline. The median increase in lesion size at 6 and 12 months was 0.5 and 1.0 disk areas in the low-dose group compared with 0 and 0 disk areas in the high-dose group. These data suggest the possibility of antiangiogenic activity that may last for several months after a single intravitreous injection of doses greater than 108 PU of AdPEDF.11. This study provides evidence that adenoviral vector-mediated ocular gene transfer is a viable approach for the treatment of ocular disorders and that further studies investigating the efficacy of AdPEDF.11 in patients with neovascular AMD should be performed.