A MULTICENTER STUDY FOR THE VALIDATION OF ALS BIOMARKERS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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。 已经鉴定了许多区分健康对照与ALS患者的重要代谢物。在血浆和脑脊液标本中，肌酸，肌酸，来自P450活性的咖啡因代谢物，肌醇和一种未命名的化合物&40;x-2546，分子量。128& 41;在区分ALS与健康对照方面具有显著的预测能力。在各种测试集中，敏感性和特异性接近80%。然而，医生不太可能难以区分ALS与健康对照，而是ALS与其他具有相似表现的神经肌肉疾病。初步研究没有足够的疾病模拟参与者进行任何有意义的统计比较。为了增加生物标志物的特异性和临床实用性，我们建议在病程早期的ALS志愿者中研究代谢组学特征，与年龄和性别匹配的其他神经肌肉疾病疾病对照相比，关闭利鲁唑和其他非必需药物。 发现早期检测ALS的生物学标志物对于评估预后和尽早开始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，研究期间采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部门的组织储存库中。

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.