Magnetic Capture of Osteoarthritis Biomarkers

骨关节炎生物标志物的磁捕获

• 批准号: 9109459
• 负责人: Kyle D Allen
• 金额: $ 31.83万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-11 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9109459
• 关键词: Address; Affect; Animal Euthanasia; Animals; Aspirate substance; Assessment tool; Behavioral; Binding; Biological Markers; Catheters; Clinic; Collection; Communication; Complex; Degenerative polyarthritis; Detection; Development; Diagnosis; Diagnostic; Disease; Early Diagnosis; Engineering; Equilibrium; Euthanasia; Fc Receptor; Future; Goals; Hand; Health; Human; Injection of therapeutic agent; Joints; Knee; Lead; Life; Link; Magnetic nanoparticles; Magnetism; Measurement; Measures; Methods; Modeling; Molecular; Monitor; Motivation; Mus; Nature; Pain; Pathogenesis; Patient-Focused Outcomes; Peer Review; Pre-Clinical Model; Procedures; Process; Prognostic Marker; Rattus; Rodent; Rodent Model; Safety; Serum; Staging; Surface; Symptoms; Synovial Fluid; Techniques; Technology; Testing; Therapeutic; Translating; United States National Institutes of Health; Urine; aptamer; base; biomarker development; biomarker discovery; biomaterial compatibility; chronic pain; design; diagnostic biomarker; disability; disabling symptom; improved; in vivo; iron oxide; joint destruction; nanoparticle; new technology; novel; novel diagnostics; particle; pre-clinical; prognostic; socioeconomics; targeted biomarker

 DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a painful, debilitating disease associated with a significant socioeconomic burden. Many potential therapeutics for OA would likely be more effective if they could be applied at early disease stages, and to facilitate this, development of diagnostics for early stage OA is a critical need for the future of OA therapy. Unfortunately, technologies to assess joint-level changes in small articular joints are underdeveloped, and these technological limits impede our ability to effectively develop new diagnostic and prognostic biomarkers for OA. Our group has developed a new magnetic nanoparticle based technology to extract biomarkers directly from small articular joints without the need to aspirate synovial fluid. Using magnetic capture, we have demonstrated the ability to detect an OA biomarker from a rat knee with greater accuracy and sensitivity than current methods. The objective of this proposal is to advance magnetic capture as a method to assess multiple biomarkers in rodent OA models following animal euthanasia (Aim 1) and as a method to assess biomarker levels in live animals (Aim 2). These advances will help enable the development of prognostic biomarkers through rodent OA models, improve the preclinical assessment of emerging OA therapeutics, and demonstrate the long-term potential to apply magnetic capture to OA biomarker analysis in small human joints, such as those of the human hand. This application focuses on two, multi-objective specific aims. In Aim 1, magnetic capture will be advanced as post mortem analysis method of joint-level OA biomarker assessment in rodents by completing the following objectives: (1.1) Develop multiplex methods to detect multiple OA biomarkers in a single magnetic capture procedure, (1.2) Refine the magnetic probe design to increase the efficiency of the magnetic nanoparticle capture, (1.3) Demonstrate feasibility and utility of magnetic capture in a mouse OA model, and (1.4) Evaluate links between joint-level OA biomarkers, histological evidence of joint degeneration, and behavioral evidence of OA symptoms. In Aim 2, magnetic capture will be advanced as an in vivo analysis method of joint-level OA biomarker assessment in rodents by completing the following objectives: (2.1) Design particles and targeting molecules for the in vivo capture of OA biomarkers, (2.2) Design a catheter-based injection/collection apparatus for the in vivo capture of magnetic nanoparticles, (2.3) Assess the clearance, safety, and biocompatibility of magnetic particles used for in vivo magnetic capture, and (2.4) Longitudinally assess a joint-level OA biomarker in the rat using in vivo magnetic capture. Successful completion of these Aims and Objectives will lead to better understand the links between OA-related pathogenesis and OA-related pain and disability, and thereby an ability to develop diagnostic and prognostic OA biomarkers that will improve patient outcomes for OA. A major step toward this goal is the development of an enabling technology for longitudinal OA biomarker assessment in the synovial fluid of small articular joints. In this proposal, our novel magnetic capture technology will be advanced to address this need.

 描述（由适用提供）：骨关节炎（OA）是一种与重要的社会经济伯恩相关的痛苦，令人衰弱的疾病。如果可以在早期疾病阶段应用它们，那么许多OA的潜在治疗剂可能会更有效，并且为了促进这一点，开发早期OA的诊断是对OA治疗的未来的迫切需求。不幸的是，评估小关节关节的联合级别变化的技术欠发达，这些技术限制阻碍了我们有效开发OA的新诊断和预后生物标志物的能力。我们的小组开发了一种新的基于磁性纳米颗粒的技术，可以直接从小关节关节中提取生物标志物，而无需抽吸滑液。使用磁捕获，我们已经证明了从大鼠膝盖中检测出比当前方法更高的精度和灵敏度的OA生物标志物的能力。该提案的目的是提高磁捕获作为一种评估动物安乐死后啮齿动物OA模型中多种生物标志物的方法（AIM 1），并作为评估活动物中生物标志物水平的方法（AIM 2）。这些进步将有助于通过啮齿动物OA模型，改善新兴OA疗法的临床前评估，使原型生物标志物的发展发展，并证明将磁捕获的长期潜力应用于小型人类关节（例如人类手的小型人类关节）。该应用程序着重于两个多目标特定的目标。 In Aim 1, magnetic capture will be advanced as post mortem analysis method of joint-level OA biomarker assessment in rodents by completing the following objectives: (1.1) Develop multiplex methods to detect multiple OA biomarkers in a single magnetic capture procedure, (1.2) Refine the magnetic probe design to increase the Effectiveness of the magnetic nanoparticle capture, (1.3) Demonstrate feasibility and utility of magnetic capture in a mouse OA model, and （1.4）评估联合OA生物标志物，联合变性的组织学证据与OA符号的行为证据之间的联系。在AIM 2中，通过完成以下目标，将作为一种体内分析方法作为一种体内分析方法来进行啮齿动物的联合级别OA生物标志物评估：（2.1）设计颗粒和靶向分子，用于体内捕获OA生物标记物，（2.2）（2.2）设计导管基于磁性的Nananoptiess（2.2），以评估基于磁性的Nananopticles（2.3），（2.2）（2.2）（2.2）用于体内磁捕获的磁性颗粒，（2.4）使用体内磁捕获在大鼠中纵向评估大鼠中的联合级OA生物标志物。这些目标和目标的成功完成将使更好地了解与OA相关的发病机理与与OA相关的疼痛和残疾之间的联系，从而有能力开发诊断和预后的OA生物标志物，从而改善OA的患者结果。朝着这一目标迈出的主要一步是开发了小关节关节滑液中纵向OA生物标志物评估的能力技术。在此提案中，我们的新型磁性捕获技术将提出来满足这一需求。