Campochiaro Peter A, Nguyen Quan Dong, Shah Syed Mahmood, Klein Michael L, Holz Eric, Frank Robert N, Saperstein David A, Gupta Anurag, Stout J Timothy, Macko Jennifer, DiBartolomeo Robert, Wei Lisa L
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Hum Gene Ther. 2006 Feb;17(2):167-76. doi: 10.1089/hum.2006.17.167.
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 10(8) 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.
28例晚期新生血管性年龄相关性黄斑变性（AMD）患者接受了单次玻璃体内注射表达人色素上皮衍生因子（AdPEDF.11）的E1、部分E3、E4缺失腺病毒载体。研究了10(6)至10(9.5)颗粒单位（PU）的剂量范围。未出现与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、短暂的眼内炎症迹象，但无严重炎症。6例患者眼压升高，通过局部用药易于控制。所有腺病毒培养均为阴性。注射后3个月和6个月，分别接受10(6)-10(7.5)PU治疗的患者中55%和50%以及接受10(8)-10(9.5)PU治疗的患者中94%和71%的病变大小与基线相比无变化或有所改善。低剂量组在6个月和12个月时病变大小的中位数增加分别为0.5和1.0个视盘面积，而高剂量组为0和0个视盘面积。这些数据表明，单次玻璃体内注射大于10(8)PU的AdPEDF.11后，可能具有持续数月的抗血管生成活性。本研究提供了证据，表明腺病毒载体介导的眼部基因转移是治疗眼部疾病的一种可行方法，应进一步开展研究以调查AdPEDF.11对新生血管性AMD患者的疗效。
