A MULTICENTER STUDY FOR THE VALIDATION OF ALS BIOMARKERS

点击翻译按钮获取中文摘要

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.