Amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease in adults, causes degeneration of both the anterior horn cells and the corticospinal tracts. Whether ALS is a single disease entity or a syndrome with diverse causes remains to be determined. ALS is poorly understood at the molecular and biochemical levels and there are currently no adequate therapies to slow its progression. In preliminary studies, we have identified a unique set of metabolic markers in ALS plasma, a finding that warrants confirmation in a larger population of ALS patients and controls. The broad goal of this proposal is expand the understanding of the pathogenesis of ALS by defining biochemical markers of the disease.
The specific aims are to 1. Collect clinical data and plasma samples from subjects with ALS and disease and non-disease comparison groups. 2. Identify unique metabolomic profiles for ALS as compared to peripheral nervous system disorders, other neurodegenerative disorders and healthy control subjects, and 3. Determine the chemical identity of some of the key metabolites in the ALS signature and use these to identify aberrant biochemical pathways in ALS. Through these investigations we will apply the techniques of metabolomics to patients with ALS to elucidate biomarkers that illuminate pathogenesis, facilitate diagnosis and potentially serve as surrogate markers in ALS therapeutic trials.