Anti-VEGF Pegylated Aptamer for Advanced Ocular Disease

抗 VEGF 聚乙二醇化适体治疗晚期眼部疾病

• 批准号: 6968625
• 负责人: EMILY Y CHEW
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6968625
• 关键词: Von Hippel Lindau syndrome; angiogenesis inhibitors; cardiovascular neoplasm; edema; eye disorder chemotherapy; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; oligonucleotides; patient oriented research; retina disorder; vascular endothelial growth factors; visual perception

Von Hippel-Lindau Syndrome (VHL) is an autosomal dominant heritable disorder in which multiple benign and malignant neoplasms and cysts of specific histopathologies develop in the kidney, adrenal gland, pancreas, brain, spinal cord, eye, inner ear, epididymis, and broad ligament. Retinal angioma may be one of the earliest manifestations of VHL disease and may lead to a significant decrease in visual acuity of the affected individual. These tumors rarely regress spontaneously. The main cause of vision loss is retinal edema, specifically macular edema secondary to enlargement of peripheral retinal angiomas or angiomas found on or around the optic disk. Treatment of retinal angiomas depends on the location and size of the lesions but typically consists of photocoagulation or cryotherapy. However, there is no proven effective therapy for the treatment of VHL ocular lesions on or surrounding the optic nerve or lesions in the peripheral retina too large to respond to the traditional therapies. The genetic mutation found in VHL disease up-regulates the production of vascular endothelial growth factor (VEGF). Immunochemical studies of the VHL ocular lesions, as well as others found elsewhere in the body show marked increase in VEGF. This open-label study will pilot the use of an anti-VEGF therapy (EYE001) in 5 patients to investigate the potential efficacy as a treatment for retinal angiomas associated with VHL. Patients will receive 6 intravitreal injections of study drug over a 30-week period, then return for a follow-up visit 1 year after initiating injections. The primary outcomes will be improvement in best corrected visual acuity of 15 letters or more at 1 year, reduction in retinal thickening and leakage at one year, changes in ERG amplitude and implicit time, and adverse events including local and systemic toxicities.

冯·希佩尔-林道综合征 (VHL) 是一种常染色体显性遗传性疾病，其中 多种良性和恶性肿瘤以及特定组织病理学的囊肿发生在 肾、肾上腺、胰腺、脑、脊髓、眼睛、内耳、附睾和广泛 韧带。视网膜血管瘤可能是 VHL 疾病的最早表现之一，并且可能 导致受影响个体的视力显着下降。这些肿瘤很少 自发回归。视力丧失的主要原因是视网膜水肿，特别是黄斑水肿 继发于周边视网膜血管瘤或周围视网膜血管瘤扩大的水肿 光盘。视网膜血管瘤的治疗取决于病变的位置和大小，但 通常包括光凝疗法或冷冻疗法。但目前尚无有效证明 用于治疗视神经上或周围的 VHL 眼部病变或视神经病变的疗法 周边视网膜太大，无法对传统疗法产生反应。发现基因突变 在 VHL 疾病中，VHL 上调血管内皮生长因子 (VEGF) 的产生。 VHL 眼部病变以及其他部位发现的其他病变的免疫化学研究 体内VEGF显着增加。这项开放标签研究将试点使用抗 VEGF 疗法（EYE001）在 5 名患者中研究作为视网膜治疗的潜在疗效 与 VHL 相关的血管瘤。患者将在一段时间内接受 6 次玻璃体内注射研究药物 30 周，然后在开始注射后 1 年后返回进行随访。初级 结果将是 1 年时最佳矫正视力提高 15 个字母或更多， 一年后视网膜增厚和渗漏减少，ERG 振幅和隐含变化 时间和不良事件，包括局部和全身毒性。