Amyotrophic lateral sclerosis (ALS), a disease of motor neuron degeneration, continues to defy treatment and the illness remains fatal. The lack of drugs is partly due to our incomplete understanding of disease mechanisms. Metabolites are a reflection of an organism’s health status. Thus, we analyzed all metabolites, otherwise known as the metabolome, in plasma from ALS patients compared to healthy people to shed light on disease mechanisms.
Comparing the metabolome in ALS patients to healthy individuals revealed several metabolic pathways that were altered in ALS. Some of these metabolic hubs may not be causative, but rather result from disease symptoms, like metabolites from muscle degeneration. Other metabolic hubs were already known to be involved in ALS pathology prior to our analysis, such as defects in lipid and amino acid metabolism. However, we also identified novel pathways, such as “xenobiotics”, i.e., chemicals that may arise from the environment, suggesting a possible involvement of toxic environmental exposure in ALS. Other altered pathways included “diacylglycerols”, a type of lipid, and “polyamine” pathways, which could potentially open new treatment avenues.