Development and Commercialization of Predictive Biomarker Panel and In-Office Kit for the Management of Diabetic Macular Edema

用于治疗糖尿病黄斑水肿的预测生物标志物组和办公室内套件的开发和商业化

• 批准号: 9406520
• 负责人: Matthew SJ Katz
• 金额: $ 21.9万
• 依托单位: OCULAR PROTEOMICS, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2019-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9406520
• 关键词: Address; Age related macular degeneration; Apoptosis; Biochemical; Biochemical Pathway; Biological Assay; Biological Markers; Brain Hypoxia-Ischemia; Cell Survival; Clinic; Clinical; Development; Device or Instrument Development; Diabetic Retinopathy; Diagnosis; Disease; Eye; Funding; Future; Immune response; Inflammation; Injectable; Lasers; Lead; Legal Blindness; Medical; Methods; Microarray Analysis; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physicians; Protein Microarray Assay; Protein Microchips; Proteins; Proteome; Proteomics; Public Health; Research; Research Project Grants; Retinal; Sampling; Small Business Innovation Research Grant; Statistical Data Interpretation; Steroids; Symptoms; Testing; Thick; Time; Treatment outcome; Vision; Visual Acuity; angiogenesis; assay development; bevacizumab; biomarker panel; commercialization; companion diagnostics; cost; design; diabetes management; diabetic; diagnostic assay; diagnostic biomarker; effective therapy; improved; macular edema; new therapeutic target; novel; outcome prediction; personalized medicine; predictive marker; predictive of treatment response; response; specific biomarkers

Abstract Diabetic Macular Edema (DME) is a vision-threatening stage in Diabetic Retinopathy (DR) that can result in legal blindness. The biochemical mechanisms that drive DME progression are not well understood and treatments address only portions of the disease pathology. The available treatment options vary widely from injectable anti- VEGF to injectable steroids to laser treatments, and carry a heavy cost burden to the US, at over $500 million per year. Currently, there are two large problems with the available treatment options: the efficacy of each treatment is highly variable from patient to patient, and sustained responses are unpredictable. Given the significant increase in diagnoses and the enormous public cost burden, there is a need to develop novel functional biomarker diagnostics which assist physicians in choosing the most effective therapy for each patient. We are developing a companion diagnostic assay for DME which can be used in a clinic setting to allow physicians to predict outcome to anti-VEGF treatment, the first-line of therapy for DME. This assay will enable personalized therapy for each DME patient, by determining appropriate therapy before DME treatment is started, when to switch treatments, and when treatment can be safely stopped (which is currently not possible). Furthermore, as the assay is composed of biomarkers specifically for DME, it can be utilized by pharmaceutical companies for discovery, development, and testing of novel or repurposed drugs for DME. We hypothesize that proteomic analysis of relevant pathways in the vitreous proteome and correlation with clinical symptoms of DME patients receiving anti-VEGF treatment will enable us to develop a predictive biomarker panel for anti-VEGF response in DME. We will use Reverse Phase Protein Microarray assay to detect proteins in vitreous samples collected from DME patients receiving anti-VEGF treatment over time. Targets to be tested include proteins associated with angiogenesis/proliferation, inflammation/ immune response, ischemia/hypoxia and apoptosis/cell survival. Statistical analysis will be performed to examine whether vitreous protein levels are correlated to changes in retinal thickness and visual acuity in response to monthly anti-VEGF treatment. The following specific aims are designed to test our hypothesis and to identify a biomarker panel that predicts treatment response: (1) Identify biochemical pathways involved in changes in retinal thickness and visual acuity in response to anti-VEGF treatment, and (2) Identify a panel of biomarkers that is predictive of changes in retinal thickness and visual acuity in response to anti-VEGF treatment Successful completion of this project will lead to the development of a predictive biomarker panel in the form of a companion diagnostic kit that assists clinicians in determining the most effective therapy for each DME patient. Furthermore, our findings will allow us to collaborate with pharma companies in development of new drug targets.

摘要 糖尿病性黄斑水肿（DME）是糖尿病性视网膜病变（DR）中威胁视力的阶段，其可导致法律的损害。 失明推动DME进展的生化机制尚未得到很好的理解， 仅涉及疾病病理学的一部分。可用的治疗选择从注射抗- VEGF到注射类固醇到激光治疗，给美国带来了超过5亿美元的沉重成本负担。 每一年。目前，可用的治疗方案存在两个大问题： 治疗因患者而异，持续的反应是不可预测的。鉴于 诊断的显著增加和巨大的公共成本负担，需要开发新的 功能性生物标志物诊断，帮助医生为每位患者选择最有效的治疗方法。 我们正在开发一种DME的伴随诊断检测方法，可用于临床环境， 医生预测抗VEGF治疗（DME的一线治疗）的结果。该分析将使 通过在DME治疗开始之前确定适当的治疗，为每位DME患者提供个性化治疗， 何时转换治疗，何时可以安全地停止治疗（目前还不可能）。 此外，由于该测定由特异性针对DME的生物标志物组成，因此其可用于药物分析。 公司的发现，开发和测试的新的或再利用的药物DME。 我们假设，玻璃体蛋白质组中相关通路的蛋白质组学分析以及与 接受抗VEGF治疗的DME患者的临床症状将使我们能够预测 DME中抗VEGF应答的生物标志物组。 我们将使用反相蛋白芯片检测从DME收集的玻璃体样品中的蛋白质 患者接受抗VEGF治疗的时间。待测试的目标包括与以下相关的蛋白质： 血管生成/增殖、炎症/免疫应答、缺血/缺氧和凋亡/细胞存活。 将进行统计学分析以检查玻璃体蛋白水平是否与玻璃体蛋白水平的变化相关。 视网膜厚度和视敏度对每月抗VEGF治疗的反应。具体目标如下： 旨在检验我们的假设并鉴定预测治疗反应的生物标志物组：（1）鉴定 抗血管内皮生长因子治疗后视网膜厚度和视敏度变化的生化途径 治疗，和（2）确定一组生物标志物，预测视网膜厚度和视觉的变化 对抗VEGF治疗的反应敏锐度 该项目的成功完成将导致预测生物标志物面板的发展， 一个配套的诊断工具包，帮助临床医生为每位DME患者确定最有效的治疗方法。 此外，我们的研究结果将使我们能够与制药公司合作开发新的药物靶点。