Discovery, Validation and Clinical Application of Novel, Non-Invasive Biomarkers

描述（由申请人提供）：UCPPS的特发性性质促使人们对该综合征的诊断和预后临床生物标志物进行了强烈的研究。开发临床相关的UCPPS生物标志物对于有效的临床管理和了解UCPPS病理，以及推进当前治疗和开发新疗法的目标至关重要。在MAPP-I期间，我们利用我们的交互式跨mapp网络的力量，使用两种不同的方法成功地确定了一组与UCPPS生物学相关的非侵入性尿液生物标志物：(1)基于该疾病的基本生物学和生理学的生物学驱动的生物标志物发现策略；(2)全球蛋白质组学生物标志物发现策略。作为MAPP生物标记物工作组的成员，我们利用自己在人类样本库开发和生物采样方面的丰富经验，与我们的同事一起制定了“最佳实践”协议，目前用于生物样本的获取、运输和储存

DESCRIPTION (provided by applicant): The idiopathic nature of UCPPS has prompted an intense search for diagnostic and prognostic clinical biomarkers of this syndrome. The development of clinically relevant biomarkers of UCPPS is critical to effective clinical management and to the understanding of UCPPS pathology, and to the goal of advancing current treatment and developing novel therapies. During MAPP-I, we have taken advantage of the power of our interactive Trans-MAPP Network to successfully identify a panel of biologically-relevant, noninvasive urinary biomarkers of UCPPS using two distinct approaches: (1) a biologically-driven biomarker discovery strategy grounded in the basic biology and physiology of this disease and (2) a global proteomics biomarker discovery strategy. As members of the MAPP Biomarker Working Group, we exploited our own extensive experience in human sample repository development and biosampling, along with that of our colleagues, to develop the 'Best Practices' protocols that are currently being utilized for the acquisition, shipping and storage of all human samples in the MAPP network. Through our directed, biologically-driven studies, we have analyzed ~500 (to date) urine samples provided during MAPP-I for the presence and amounts of six different protein biomarkers identified as described above. In addition to the identification and validation of these individual protein biomarkers, we also found that (1) UCPPS significantly changes the urinary proteome as compared to that of healthy and positive controls and (2) UCPPS may alter the regulation of extracellular matrix proteins in a definable, biologically-relevant pattern. We are now in the process of completing the validation studies of those urinary proteins identified in our global proteomics work and intend to multiplex them with those discovered through our biologically-driven discovery studies. We will then combine our final validated panel of biomarkers with biologic and clinical data from other participating MAPP discovery sites. Multiplexing these markers will increase the predictive power of any of the markers alone. We will then test the ability of this panel of biomarkers to identify the presence o UCPPS, monitor response to therapy, predict disease progression and episodic flares, and confirm improvement and resolution, with or without intervention. Finally, we will ask what these validated diagnostic targets teach us about mechanism(s) underlying these different UCPPS disease stages. These goals will be met within the context of the following Specific Aims: Aim 1 To assess the utility of the identified and validated urinary biomarkers from Phase I in the clinical management of UCPPS Aim 2 To assess the clinical utility of multiplexing all biomarkers validated in our studies with biologic and clinical data identified and validated by other Trans-MAPP groups Aim 3 To elucidate the mechanism(s) underlying the presence of disease, disease flare, response to intervention and resolution