A MULTICENTER STUDY FOR THE VALIDATION OF ALS BIOMARKERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 一些重要的代谢物已经被识别出来，以区分健康对照和ALS患者。在血浆和脑脊液样本中，肌酸、肌酐、P450活性咖啡因的代谢物肌醇和一种未命名的化合物&&#35；40；x-2546，M.W.128；在区分肌萎缩侧索硬化症和健康对照方面具有显著的预测能力。在不同的测试集上，灵敏度和特异度均接近80%。然而，医生不太可能难以区分ALS与健康对照，而是ALS与其他具有类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来进行任何有意义的统计比较。为了提高生物标记物的特异性和临床实用性，我们建议研究ALS志愿者病程早期的代谢特征，停用利鲁唑和其他非必要药物，并与年龄和性别匹配的疾病对照和其他神经肌肉疾病进行比较。 发现早期发现ALS的生物学标志物对评估预后和尽早应用神经保护药物至关重要。代谢组学是了解疾病机制和开发可能的生物标志物的一种可能的方法。还有其他技术可以为疾病状态及其进展提供生物标记物。因此，在研究期间收集的部分样本将用于新陈代谢研究，其余的将储存在神经学临床试验单位的组织储存库中。

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.