Development and Commercialization of Ocular Diagnostic Test Based on Vitreous Pro

描述（由申请人提供）：年龄相关性黄斑变性（AMD）是发达国家60岁以上人群视力丧失和失明的主要原因。这种疾病的进展导致丧失与生活质量高度相关的活动能力。这种疾病的进展尚不清楚，治疗方法仅针对疾病的部分潜在机制，而无法治愈。目前的治疗标准是重复玻璃体内抗血管内皮生长因子（anti-VEGF）药物治疗。然而，只有34-40%的患者获得了临床上显著的视力，并在一到两年的时间里保持了这种视力。眼部蛋白质组学有限责任公司（OPL）的目标是验证一组生物标志物，以预测抗vegf治疗的临床无反应，使医生能够快速识别那些将从替代疗法中受益的患者。目前的方法是另一种选择，只有在几个月的无效治疗后才能确定无反应。OPL实验室先前在人眼的玻璃体液中发现了细胞受体及其磷酸化（活化）形式的存在。在抗vegf治疗应答者和无应答者之间，一些蛋白的数量有显著差异。OPL的方法一直集中在使用rp.p.m.（逆相蛋白质微阵列）技术来准确区分患者的不同疾病状态。此外，最近的发现表明，在一些小的疾病群体中，患者亚群之间存在数量差异。下一阶段是利用这些过去的发现来揭示反应性和非反应性患者之间的其他差异。长期目标包括在更大的人群中验证这些独特的数量差异，以及传播疾病进展的分子机制。从这些目标中获得的结果将导致使用诊断玻璃体蛋白质组预测反应性视网膜疾病，包括湿性AMD。本提案的具体目的包括：1)从全国多个视网膜中心招募湿性AMD患者参与研究2)验证潜在生物标志物预测治疗反应和疾病进展的有效性3)确定确定和预测治疗反应和疾病进展的最重要的AMD生物标志物

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 60 in the developed world. Progression of this disease results in the loss of the ability to perform activities highly correlaed with quality of life. This disease progression is not well understood and treatments address only portions of the underlying mechanisms of the disease, while there is no cure. The current standard of care is repetitive intravitreal anti-vascular endothelial growth factor (anti-VEGF) pharmacologic treatment. However, only 34-40% of patients gain clinically significant vision and maintain that gain over the course of one to two years. Ocular Proteomics, LLC (OPL)'s objective is to validate a panel of biomarkers that predict clinical non-responders to anti-VEGF therapy to allow physicians to quickly identify those who would benefit from alternative therapies. The current methodology is the alternative, where non-responders are identified only after months of ineffective treatment. The OPL lab previously discovered the presence of cell receptors and their phosphorylated (activated) forms in the vitreous fluid of human eyes. Significant quantitative differences in several proteins between anti-VEGF treatment responders and non-responders were demonstrated. OPL's approach has been centered on the use of R.P.P.M. (reverse-phase protein microarray) technology to accurately discriminate different disease states in patients. Also, recent discoveries show quantitative differences between subsets of patients within some small disease groups. The next phase is to employ these past discoveries to uncover additional differences between responsive and non-responsive patients. Long term objectives include validating these unique quantitative differences among larger populations, as well as disseminating the molecular mechanisms of disease progression. The results achieved from these objectives will lead to predicting response retinal diseases, including wet AMD using the Diagnostic Vitreous Proteome. The specific aims of this proposal include: 1) Recruit patients with wet AMD from multiple retina centers across the country to participate in the study 2) Validate Efficacy of potential Biomarkers to Predict Treatment Response and Disease Progression 3) Finalize most significant AMD biomarkers for determining and predicting Treatment Response and Disease Progression