Multi-Center Validation of Biomarkers for Motor Neuron Disease

运动神经元疾病生物标志物的多中心验证

基本信息

批准号：
7935499
负责人：
ROBERT P BOWSER
金额：
$ 38.53万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-09-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7935499
关键词：
Address Adult Age Amyotrophic Lateral Sclerosis Antibodies Area Autoimmune Process Award Biological Assay Biological Markers Blood Blood specimen Cerebrospinal Fluid Clinic Clinical Investigator Clinical Research Clinical Trials Collection Communities Country Degenerative Disorder Development Diagnosis Diagnostic Diagnostic tests Employee Strikes Enzyme-Linked Immunosorbent Assay Goals In Vitro Inflammatory Mass Spectrum Analysis Mediating Medical center Monitor Motor Neuron Disease Motor Neurons Neurologic Orphan Disease Patients Plasma Positioning Attribute Procedures Prospective Studies Proteins Research Ethics Committees Sampling Spinal Cord Standardization Testing Time Validation base clinical research site disorder control drug efficacy experience multiple reaction monitoring novel public health relevance research study sample collection validation studies

项目摘要

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (03) Biomarker Discovery and Validation, and specific Challenge Topic 03-NS-102: Standardization and validation of neurologic biomarkers. While many studies have identified putative protein based biomarkers for amyotrophic lateral sclerosis (ALS), all have used a limited number of total test subjects. Therefore large validation studies are required to confirm these potential biomarkers for ALS. Such validated biomarkers can then be advanced towards the clinic within diagnostic tests and assays to monitor drug efficacy in clinical trials. Since ALS is an orphan disease, multi-center clinical research studies are required to obtain the necessary number of patient and control samples in order to properly validate biomarkers for ALS. We are uniquely positioned to rapidly advance multi-center biomarker validation studies for ALS. We have established standard operating procedures for the collection of blood plasma and cerebrospinal fluid (CSF) samples. During the past year we have created a consortium of 20 medical centers and ALS clinics with IRB approval to utilize these standardized sample collection procedures. This consortium of clinics and clinical investigators includes many of the leaders within the ALS community. We hypothesize that select protein and antibody based biomarkers will be validated in a large, prospective study using CSF and blood samples from multiple clinics throughout the country. To test this hypothesis, we propose three specific aims that address a key challenge to initiate and rapidly advance a multi-center biomarker validation study for ALS. The first specific aim will collect biofluid samples using standard operating procedures at 20 ALS clinics throughout the country. The second aim is to perform a targeted ELISA and mass spectrometry based multiple reaction monitoring (MRM) assays to validate specific protein biomarkers for ALS. The final aim will use these same biofluid samples to validate the presence of specific antibodies to spinal cord proteins in ALS patients. This study will validate specific protein and antibody based biomarkers for ALS that will assist in the development of in vitro diagnostic assays for ALS. Given the experience of our collaborative team, we are confident in our ability to complete the proposed studies within the 2-year time frame of the Challenge Award. PUBLIC HEALTH RELEVANCE: The overall goal of the proposed study is to validate specific biomarkers for amyotrophic lateral sclerosis (ALS). ALS is a fatal motor neuron degenerative disease that can strike adults of any age, yet we know little about its causes and cannot rapidly diagnose ALS. Our validated protein and antibody based biomarkers for ALS will create quick diagnostic tests for ALS.

描述（由申请人提供）：本申请涉及广泛的挑战领域 (03) 生物标志物发现和验证，以及具体的挑战主题 03-NS-102：神经系统生物标志物的标准化和验证。虽然许多研究已经确定了肌萎缩侧索硬化症 (ALS) 的推定蛋白质生物标志物，但所有研究都使用了有限数量的总测试对象。因此，需要进行大型验证研究来确认这些潜在的 ALS 生物标志物。然后，这些经过验证的生物标志物可以在诊断测试和测定中推进临床，以监测临床试验中的药物疗效。由于 ALS 是一种孤儿疾病，因此需要进行多中心临床研究以获得必要数量的患者和对照样本，以便正确验证 ALS 的生物标志物。我们拥有独特的优势，可以快速推进 ALS 的多中心生物标志物验证研究。我们制定了血浆和脑脊液 (CSF) 样本采集的标准操作程序。去年，我们创建了一个由 20 个医疗中心和 ALS 诊所组成的联盟，并获得 IRB 的批准，以利用这些标准化样本采集程序。这个诊所和临床研究人员联盟包括 ALS 界的许多领导者。我们假设基于蛋白质和抗体的生物标记物将在一项大型前瞻性研究中使用来自全国多个诊所的脑脊液和血液样本进行验证。为了检验这一假设，我们提出了三个具体目标，以应对启动和快速推进 ALS 多中心生物标志物验证研究的关键挑战。第一个具体目标是使用标准操作程序在全国 20 个 ALS 诊所收集生物流体样本。第二个目标是进行基于 ELISA 和质谱的多反应监测 (MRM) 检测，以验证 ALS 的特定蛋白质生物标志物。最终目标将使用这些相同的生物流体样本来验证 ALS 患者中是否存在针对脊髓蛋白的特异性抗体。这项研究将验证基于特定蛋白质和抗体的 ALS 生物标志物，这将有助于 ALS 体外诊断测定的开发。鉴于我们合作团队的经验，我们对在挑战奖的 2 年期限内完成拟议研究的能力充满信心。公共健康相关性：拟议研究的总体目标是验证肌萎缩侧索硬化症 (ALS) 的特定生物标志物。 ALS 是一种致命的运动神经元退行性疾病，可侵袭任何年龄段的成年人，但我们对其病因知之甚少，无法快速诊断 ALS。我们经过验证的基于蛋白质和抗体的 ALS 生物标志物将为 ALS 创建快速诊断测试。