A MULTICENTER STUDY FOR THE VALIDATION OF ALS BIOMARKERS

验证 ALS 生物标志物的多中心研究

• 批准号: 8167046
• 负责人: JAMES B CARESS
• 金额: $ 1.21万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167046
• 关键词: Age; Biological Markers; Biological Markers; Caffeine; Clinical; Clinical Trials Unit; Computer Retrieval of Information on Scientific Projects Database; Creatine; Creatinine; Cytochrome P450; Disease; Early Diagnosis; Funding; Gender; Grant; Inositol; Institution; Methods; Multicenter Studies; Neurology; Neuromuscular Diseases; Neuroprotective Agents; Participant; Patients; Pharmaceutical Preparations; Physicians; Plasma; Research; Research Personnel; Resources; Rest; Riluzole; Sampling; Sensitivity and Specificity; Source; Specificity; Specimen; Technology; Testing; Tissues; United States National Institutes of Health; Validation; disorder control; insight; metabolomics; outcome forecast; repository; volunteer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A number of significant metabolites that distinguish healthy controls from ALS patients have been identified. In both plasma & CSF specimens, Creatine, Creatinine, metabolites of caffeine from P450 activity, Inositol and an unnamed compound (x-2546, m.w. 128) had significant predictive power in differentiating ALS from healthy controls. The sensitivity and specificity approached 80% in various test sets. However, it is unlikely that physicians will have difficulty-distinguishing ALS from healthy controls but rather ALS from other neuromuscular disorders with similar presentations. Preliminary studies did not have enough disease mimic participants to make any meaningful statistical comparisons. To increase the specificity and clinical utility of the biomarkers, we propose to study metabolomic signatures in a new subset of volunteers with ALS early in the disease course, off riluzole and other non-essential medications, compared to age and gender matched disease controls with other neuromuscular diseases. Discovering biological markers for early detection of ALS is critical to evaluate prognosis and to start neuroprotective drugs as early as possible. Metabolomics is one possible method to gain insight into mechanisms of disease and develop possible biomarkers. There are other technologies that may provide biomarkers for the disease state and its progression. Therefore a portion of the samples collected during the study will be utilized for metabolomic studies and the rest will be stored in a tissue repository at the Neurology Clinical Trials Unit.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 已鉴定出许多区分健康对照和 ALS 患者的重要代谢物。在血浆和脑脊液样本中，肌酸、肌酐、P450 活性的咖啡因代谢物、肌醇和未命名的化合物 (x-2546，m.w. 128)在区分 ALS 与健康对照方面具有显着的预测能力。各种测试集的敏感性和特异性均接近 80%。然而，医生不太可能难以将 ALS 与健康对照者区分开来，而是将 ALS 与具有类似表现的其他神经肌肉疾病区分开来。初步研究没有足够的疾病模拟参与者来进行任何有意义的统计比较。为了提高生物标志物的特异性和临床实用性，我们建议在病程早期研究一组新的 ALS 志愿者的代谢组学特征，并与年龄和性别匹配的疾病对照和其他非必需药物进行比较。神经肌肉疾病。 发现早期检测 ALS 的生物标志物对于评估预后和尽早开始使用神经保护药物至关重要。代谢组学是深入了解疾病机制和开发可能的生物标志物的一种可能方法。还有其他技术可以为疾病状态及其进展提供生物标志物。因此，研究期间收集的部分样本将用于代谢组学研究，其余样本将储存在神经病学临床试验单位的组织储存库中。