Identification of Protein Biomarkers for ALS

DESCRIPTION (provided by applicant): The long term goal of the proposed study is to identify reliable and accurate biomarkers for diagnosis, assessment of disease progression, and evaluation of clinial trials in amyotrophic lateral sclerosis (ALS). We will use chemical modification approaches to reveal differences in protein conformation between normal and ALS samples, and detect them via Western and 2D protein electrophoresis analyses. We have discovered a 35 kD protein species that is uniquely present in ALS but not in normal spinal cord samples. We have also observed a pattern of protein spots on the 2D gel that is present in ALS but not in normal spinal cord samples. The specific aims for this application are first to determine independently whether either of two molecular signatures identified in the spinal cord can be observed in peripheral non-invasive tissues such as muscle and blood specimens. Second, we will try to develop qualitative and quantitative tests based on the indenfied biomarkers for ALS for potential diagnosis, assessment of disease progression, and evaluation of clinical trials in ALS. Two steps will be taken to acchieve the second aim. Standard criteria for tests will be esablished using known ALS samples. These crtiteria will then be used to identify unknown samples (to the testers) to assess the sensitivity and accuracy of the tests using identified biomarkers in ALS.