Inhibition of Migration for PVR Treatment

抑制迁移以进行 PVR 治疗

• 批准号: 6993953
• 负责人: EUGENE G LEVIN
• 金额: $ 10万
• 依托单位: MOTILITY, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6993953
• 关键词: disease /disorder model; drug screening /evaluation; eye agent; eye disorder chemotherapy; laboratory rabbit; nonhuman therapy evaluation; pharmacokinetics; proliferative vitreoretinopathy

DESCRIPTION (provided by applicant): Proliferative vitreoretinopathy (PVR) is the principal cause of failed retinal detachment surgery. PVR is characterized by the migration and proliferation of retinal pigment cells, fibroblasts, glial cells, and inflammatory cells on or beneath the retina or in the vitreous cavity. This leads to the formation of contractile cellular membranes which cause retinal detachment. Attempts to treat PVR have involved the use of antimetabolites and steroids. None of these options have come into routine clinical use and current interventions are limited to surgical treatment. While inhibition of cell proliferation has been the focus of the development of drugs to treat PVR, the possibility that cell migration, which plays as important of a role, would be another potential target. We have developed a small molecular weight protein (LD22-4) that inhibits the migration of a number of different cell types in vitro and in vivo. Because of the importance of cell migration in the development of PVR and the proven effectiveness of LD22-4 in vivo, we performed pilot studies of the effect of the protein in a rabbit model of PVR. The results clearly showed that LD22-4 inhibited the development of PVR in each animal that received the protein. Based on these considerations, we propose a more extensive evaluation of the effects of LD22-4 on PVR. The Phase I project will include two Specific Aims: 1. Dose titration analysis to establish effective doses for maximum inhibition of PVR 2. Time course study to determine the minimum number of injections needed to inhibit PVR. These results will provide the basis for the eventual use of LD22-4 in the treatment of PVR.

描述（由申请人提供）：复发性玻璃体视网膜病变（PVR）是视网膜脱离手术失败的主要原因。PVR的特征在于视网膜色素细胞、成纤维细胞、神经胶质细胞和炎性细胞在视网膜上或视网膜下或玻璃体腔中的迁移和增殖。这导致形成可收缩的细胞膜，从而导致视网膜脱离。治疗PVR的尝试涉及抗代谢药和类固醇的使用。这些选择都没有进入常规临床使用，目前的干预措施仅限于手术治疗。虽然抑制细胞增殖一直是治疗PVR的药物开发的焦点，但细胞迁移的可能性（其起着同样重要的作用）将是另一个潜在的靶点。我们已经开发了一种小分子量蛋白质（LD 22 -4），它在体外和体内抑制许多不同细胞类型的迁移。由于细胞迁移在PVR发展中的重要性和LD 22 -4在体内的有效性，我们在PVR的兔模型中进行了蛋白质作用的初步研究。结果清楚地表明，LD 22 -4抑制了接受蛋白质的每只动物中PVR的发展。基于这些考虑，我们建议对LD 22 -4对PVR的影响进行更广泛的评估。第一阶段项目将包括两个具体目标： 1.剂量滴定分析，以确定最大抑制PVR的有效剂量 2.确定抑制PVR所需的最小注射次数的时程研究。 这些结果将为LD 22 -4在PVR治疗中的最终应用提供依据。