Development and Commercialization of Ocular Diagnostic Tests Based on Vitreous Pr

基于玻璃体PR的眼部诊断测试的开发和商业化

• 批准号: 8003379
• 负责人: Bert Glaser
• 金额: $ 17.74万
• 依托单位: OCULAR PROTEOMICS, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003379
• 关键词: Address; Age; Age related macular degeneration; Alternative Therapies; Anti-Inflammatory Agents; Antibodies; Biological Markers; Blindness; Chronic; Clinical; Clinical Trials; Control Groups; Degenerative Disorder; Deterioration; Development; Diagnostic; Diagnostic tests; Disease; Disease Management; Disease Progression; Eye; Eye diseases; Facilities and Administrative Costs; Group Identifications; Human; Individual; Inflammatory; Lead; Libraries; Liquid substance; Medicine; Microarray Analysis; Modeling; Optical Coherence Tomography; Pathway interactions; Patient Rights; Patients; Pharmaceutical Preparations; Phase; Physicians; Process; Protein Microchips; Proteins; Proteome; Proteomics; Public Health; Quality of life; Receptor Cell; Research; Retina; Retinal Diseases; Retinal Vein Occlusion; Risk; Sampling; Sampling Studies; Testing; Therapeutic; Time; Treatment Failure; Validation; Vascular Endothelial Growth Factors; Vision; Visual; Visual Acuity; angiogenesis; base; clinically significant; cohort; commercialization; cost; diabetic; improved; innovation; macular edema; novel strategies; prospective; public health relevance; research study; response; standard of care; tool

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 correlated with quality of life. The disease process is not well understood. Treatments address only portions of the underlying mechanisms of the disease and there is no cure. The current standard of care is repeated 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. Currently non-responders are identified only after months of ineffective treatment. Our objective is to validate a panel of biomarkers that predict clinical non-responders to anti-VEGF monotherapy so that physicians can quickly identify patients who would benefit from alternative therapy rather than waiting for months to clinically demonstrate treatment failure before implementing these other therapeutic strategies. We have discovered the presence of cell receptors and their activated phosphorylated forms in the vitreous fluid of human eyes and that there are significant protein level differences between anti-VEGF treatment responders and non-responders. Ocular Proteomics, LLC (OPL)'s approach will be based on the use of reverse-phase protein microarray (RPPM) technology to accurately discriminate different disease states in at-risk patients. OPL is at the forefront of a small group that uses RPPM technology to investigate biomarkers for degenerative ocular diseases. Results will lead the way for this project to study the predictive potential of the vitreous proteome for retinal diseases, including wet AMD. Hypotheses 1) The baseline proteome of wet AMD patients is distinctive from that of healthy normals or patients with other types of eye diseases. 2) The baseline vitreous proteome of wet AMD non-responders to anti-VEGF therapy differs significantly from that of wet AMD responders. 3) Differences in the baseline proteome of responders and non-responders are likely to lie in proteins involved in the VEGF, angiogenesis, and/or inflammatory pathways. The Specific Aims of the proposal are: (Aim 1) use model of clinical response to form cohorts of vitreous samples for biomarker analysis, (Aim 2) profile candidate vitreous biomarkers using antibody microarrays, and (Aim 3) validate and quantify the biomarkers. PUBLIC HEALTH RELEVANCE: The proposed research will improve public health by improving the vision of patients with wet age-related macular degeneration at reduced costs. It will do this by producing a product that will allow retina physicians to perform a test that will determine how a patient will respond to a given treatment before starting the patient on this treatment. This will allow the doctor to choose the right treatment for the right patient at the right time, providing truly personalized medicine.

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。疾病的过程还不太清楚。治疗只能解决疾病的部分潜在机制，并且没有治愈方法。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。目前，只有在几个月的无效治疗后才能确定无反应者。我们的目标是验证一组生物标志物，这些生物标志物可预测抗VEGF单药治疗的临床无应答者，以便医生能够快速识别将从替代疗法中获益的患者，而不是在实施这些其他治疗策略之前等待数月以临床证明治疗失败。我们已经发现在人眼的玻璃体液中存在细胞受体及其活化的磷酸化形式，并且在抗VEGF治疗应答者和无应答者之间存在显著的蛋白质水平差异。眼蛋白质组学有限责任公司（OPL）的方法将基于使用反相蛋白质微阵列（RPPM）技术，以准确区分风险患者的不同疾病状态。OPL是一个小组的最前沿，该小组使用RPPM技术研究退行性眼病的生物标志物。结果将为该项目研究玻璃体蛋白质组对视网膜疾病（包括湿性AMD）的预测潜力开辟道路。假设1）湿性AMD患者的基线蛋白质组不同于健康正常人或患有其他类型的眼部疾病的患者。2)抗VEGF治疗无效的湿性AMD患者的基线玻璃体蛋白质组与湿性AMD有效者的基线玻璃体蛋白质组显著不同。3)应答者和非应答者的基线蛋白质组的差异可能在于参与VEGF、血管生成和/或炎症途径的蛋白质。该提案的具体目的是：（目的1）使用临床反应模型来形成玻璃体样本队列以进行生物标志物分析，（目的2）使用抗体微阵列来分析候选玻璃体生物标志物，以及（目的3）验证和量化生物标志物。 公共卫生相关性：这项拟议中的研究将通过以较低的成本改善湿性年龄相关性黄斑变性患者的视力来改善公众健康。它将通过生产一种产品来实现这一点，该产品将允许视网膜医生进行测试，以确定患者在开始这种治疗之前对给定治疗的反应。这将使医生能够在正确的时间为正确的患者选择正确的治疗方法，提供真正的个性化医疗。