Qualification of Prognostic and Diagnostic Biomarkers of Knee Osteoarthritis

膝骨关节炎的预后和诊断生物标志物的鉴定

• 批准号: 9289779
• 负责人: Virginia Kraus
• 金额: $ 68.94万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9289779
• 关键词: African American; Age; Analgesics; Appearance; Biochemical; Biochemical Markers; Biological Markers; Blood Tests; Body mass index; Caucasians; Clinical; Clinical Trials; County; Degenerative polyarthritis; Diagnosis; Diagnostic; Diagnostic radiologic examination; Early identification; Early treatment; Enzyme-Linked Immunosorbent Assay; Evaluation; Failure; Female; Foundations; Future; Goals; Hand; Hip region structure; Image; Individual; Inflammatory; Joints; Kellgren-Lawrence grade; Knee; Knee Osteoarthritis; Knee joint; Magnetic Resonance Imaging; Measures; Modeling; Modification; Pain; Pathologic Processes; Patients; Peptides; Persistent pain; Pharmaceutical Preparations; Phenotype; Prognostic Marker; Proteins; Proteomics; Race; Reporting; Risk; Sampling; Serum; Symptoms; Synovial Fluid; Testing; United States Food and Drug Administration; United States National Institutes of Health; Urine; Vertebral column; Width; Woman; Work; base; biomarker panel; candidate marker; clinical predictors; clinically relevant; cohort; combinatorial; cost; design; diagnostic biomarker; drug development; follow-up; high risk; improved; interest; joint injury; knee pain; men; multiple reaction monitoring; predictive marker; secondary outcome; sex; success; tool; tool development

Abstract A cure for osteoarthritis (OA) remains elusive. This is due in large part to two major obstacles, inability to detect OA sufficiently early before the onset of irreversible signs and recalcitrant symptoms, and inability to identify individuals at high risk of progression based on traditionally used metrics (age, sex, body mass index, knee pain and joint space width). The latter challenge is responsible for low powering of clinical trials and numerous drug trial failures. Using a systematic, unbiased and iterative approach, we have created a multiple reaction monitoring (MRM) proteomic panel for serum-based prediction of knee OA structural progression and diagnosis of knee OA. The selection of proteins was based on results of extensive discovery proteomic studies in synovial fluid, urine, and serum from knee OA radiographic progressors and non-progressors (with 3-4 year follow-up) and controls. The ultimate goals of this work are to qualify these new biomarker candidates in the contexts of knee OA progression and OA diagnosis in larger well-phenotyped cohorts from the Osteoarthritis Initiative, the Johnston County Osteoarthritis Project and the Chingford cohorts. With this further qualification, these new biomarker tools will be very significant for their potential utility for clinical trial and clinical use to inform strategies for phenotyping and earlier identification and treatment of OA patients. We also intend to pursue formal Food and Drug Administration (FDA) qualification of the optimal marker set yielded by this proposal to facilitate their use as drug development tools.

抽象的 骨关节炎（OA）的治愈方法仍然难以捉摸。这在很大程度上是由于两个主要障碍，即无法 在不可逆体征和顽固症状出现之前及早发现 OA，并且无法及时治疗 根据传统使用的指标（年龄、性别、体重指数、 膝盖疼痛和关节间隙宽度）。后一个挑战是导致临床试验效率低下的原因 多次药物试验失败。使用系统的、公正的和迭代的方法，我们创建了一个多重 反应监测 (MRM) 蛋白质组组用于基于血清的膝关节 OA 结构进展预测 膝关节骨关节炎的诊断。蛋白质的选择基于广泛发现的蛋白质组学研究的结果 膝关节 OA 放射学进展者和非进展者（3-4 年）的滑液、尿液和血清中含有 后续）和控制。这项工作的最终目标是使这些新的候选生物标志物具有资格 骨关节炎较大表型队列中膝关节 OA 进展和 OA 诊断的背景 倡议、约翰斯顿县骨关节炎项目和 Chingford 队列。有了这个进一步的资格， 这些新的生物标志物工具对于临床试验和临床使用的潜在效用将非常重要。 为 OA 患者的表型分析以及早期识别和治疗策略提供信息。我们也打算 寻求由此产生的最佳标记集的正式食品和药物管理局 (FDA) 资格 促进其用作药物开发工具的提案。