Magnetic Collection of Joint-Level Osteoarthritis Biomarkers

关节级骨关节炎生物标志物的磁性收集

• 批准号: 8735614
• 负责人: Kyle D Allen
• 金额: $ 15.27万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-16 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8735614
• 关键词: Affect; Aging; American; Animal Model; Antibodies; Antibody Dissociations; Binding; Biological Markers; Calibration; Chronic; Clinic; Clinical; Collection; Degenerative polyarthritis; Development; Development Plans; Diagnosis; Diagnostic; Disease; Early Diagnosis; Epidemic; Expenditure; Facet joint structure; Goals; Harvest; Healthcare; Human; In Vitro; Irrigation; Joints; Knee; Knee Osteoarthritis; Liquid substance; Magnetism; Medial meniscus structure; Methods; Modeling; Molecular; Molecular Analysis; Motivation; Needles; Obesity; Patients; Pharmaceutical Preparations; Population; Property; Proteins; Proxy; Rattus; Recovery; Research; Rodent Model; Serum; Severities; Simulate; Staging; Surface; Synovial Fluid; Techniques; Technology; Therapeutic; Translating; Uninsured Medical Expense; United States; Urine; Vertebral column; Work; antibody conjugate; arthropathies; base; burden of illness; clinical practice; clinically relevant; hand interphalangeal joint; innovation; joint destruction; lifestyle intervention; magnetic field; molecular marker; nanoparticle; novel; particle; patient population; pre-clinical; prevent; public health relevance; research study; socioeconomics; technology development; tool

DESCRIPTION (provided by applicant): The 2007 aggregate healthcare expenditures attributed to osteoarthritis (OA) treatment in the United States were $185 billion, with an average out-of-pocket expense for an OA patient of approximately $2600 annually (the equivalent of 3 wks pay for an average American citizen). Moreover, the OA patient population is anticipated to grow from 27 million patients to 67 million patients in 2030, due to an aging US population and an epidemic of obesity. Despite this significant and growing socioeconomic burden, disease modifying OA drugs (DMOADs) have been difficult to translate from the lab to the clinic. The lack of DMOADs is due in part to an inability to detect early-stage OA, a disease stage where interventions and lifestyle changes have greater potential to reverse a chronic cascade of joint destruction found in the OA-affected joint. Clinically, OA is diagnosed through radiographs and physical exams, yet these diagnostics are relatively poor at detecting early-stage OA. A significant need exists for technologies that facilitate early-stage OA diagnosis. Molecular biomarkers have tremendous potential to diagnose OA prior to the development of structural damage in the joint (pre-radiographic). The goal of this proposal is to develop a novel magnetic nanoparticle-based technique to collect OA biomarkers from synovial fluid without the need to remove fluid from the joint space. Using magnetic harvesting, potential molecular markers of joint destruction can be removed from the synovial fluid and quantified to examine the severity of joint disease. Moreover, because the technique can work in a wide range of joint fluid volumes, biomarkers could be quantified in both preclinical rodent models of OA and in the clinical setting. The proposal goal will be achieved through two specific aims. Aim 1 is to develop an enhanced, quantitative technique (magnetic harvesting) for the joint-level collection of OA biomarkers in vitro. Aim 1 will be achieved through three sub-aims: 1) Define key parameters for magnetic harvesting in vitro, 2) Investigate and experimentally verify models to relate the amount of biomarker collected via magnetic harvesting to the initial biomarker concentration within synovial fluid, and 3) Assess the sensitivity of magnetic harvesting in a phantom human knee. Aim 2 is to collect and analyze joint-level biomarkers in a rat model of knee OA using magnetic harvesting. Aim 2 will examine the utility of magnetic harvesting as a research tool for small animal models, comparing magnetic harvesting to other available methods to recover joint-level proteins for molecular analysis (lavage, fluid wicking). The immediate impact of this work will be the development of an innovative research tool that will enable the quantitative assessment of multiple joint-level molecular biomarkers in small animal models of OA. The long-term impact of this work is the potential to develop new methods to diagnosis early-stage OA and the development of a technology that would enable biomarker analysis in smaller human joints affected by OA, including the metacarpophalangeal and interphalangeal joints of the hand and the facet joints of the spine.

描述（由申请人提供）：2007年，美国用于骨关节炎（OA）治疗的总医疗支出为1850亿美元，OA患者的平均自付费用约为每年2600美元（相当于普通美国公民3周的费用）。此外，由于美国人口老龄化和肥胖症的流行，预计OA患者人群将从2700万患者增长到2030年的6700万患者。尽管有这种显著且不断增长的社会经济负担，但疾病修饰OA药物（DMOAD）很难从实验室转化为临床。DMOAD的缺乏部分是由于无法检测早期OA，这是一个疾病阶段，干预和生活方式的改变更有可能逆转OA受影响关节中发现的慢性关节破坏级联。在临床上，OA是通过X光片和身体检查诊断，但这些诊断在检测早期OA相对较差。对于促进早期OA诊断的技术存在巨大需求。分子生物标志物具有巨大的潜力，可以在关节结构损伤发生之前（放射学检查前）诊断OA。该提案的目标是开发一种新的基于磁性纳米颗粒的技术，以从滑液中收集OA生物标志物，而无需从关节间隙中去除液体。使用磁采集，可以从滑液中去除关节破坏的潜在分子标记物，并对其进行定量，以检查关节疾病的严重程度。此外，由于该技术可以在广泛的关节液体积中工作，因此可以在OA的临床前啮齿动物模型和临床环境中定量生物标志物。该提案的目标将通过两个具体目标实现。目的1是开发一种增强的定量技术（磁收获），用于体外关节水平收集OA生物标志物。目标1将通过三个子目标实现：1）定义体外磁采集的关键参数，2）研究和实验验证模型，以将通过磁采集收集的生物标志物的量与滑液中的初始生物标志物浓度相关联，以及3）评估人体膝关节体模中磁采集的灵敏度。目的2是使用磁采集在膝关节OA大鼠模型中收集和分析关节水平的生物标志物。目标2将研究磁收集作为小动物模型研究工具的实用性，将磁收集与其他可用的方法进行比较，以恢复关节水平的蛋白质进行分子分析（灌洗，液体芯吸）。这项工作的直接影响将是开发一种创新的研究工具，该工具将能够定量评估OA小动物模型中的多种关节水平分子生物标志物。这项工作的长期影响是有可能开发新的方法来诊断早期OA，并开发一种技术，使生物标志物分析在受OA影响的较小的人体关节，包括手的掌指关节和指间关节以及脊柱的小关节。