Development and Commercialization of Ocular Diagnostic Test Based on Vitreous Pro

描述（由申请人提供）：视网膜相关性黄斑变性（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。这种疾病的进展还没有得到很好的理解，治疗方法只解决了疾病的部分潜在机制，而没有治愈。目前的标准治疗是重复玻璃体内抗血管内皮生长因子（抗VEGF）药物治疗。然而，只有34-40%的患者获得临床显著的视力，并在一到两年的时间内保持这种增益。眼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，预测抗VEGF治疗的临床无应答者，使医生能够快速识别那些从替代疗法中受益的人。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者。OPL实验室先前发现了人眼玻璃体液中存在细胞受体及其磷酸化（活化）形式。证明了抗VEGF治疗应答者和无应答者之间几种蛋白质的显著定量差异。OPL的方法一直集中在使用R. P. P.M.（反相蛋白质微阵列）技术，以准确区分患者的不同疾病状态。此外，最近的发现表明，在一些小的疾病组内的患者子集之间存在定量差异。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。长期目标包括验证较大人群中这些独特的定量差异，以及传播疾病进展的分子机制。从这些目标获得的结果将导致使用诊断性维生素蛋白质组预测视网膜疾病的反应，包括湿性AMD。该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）评估潜在生物标志物预测治疗反应和疾病进展的有效性3）最终确定用于确定和预测治疗反应和疾病进展的最重要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