Comparison of Etomoxir, a lipid metabolism blocker, and interferon-β treatment on antibody recognition of brain proteins in Multiple Sclerosis

Background: The pathogenesis of Multiple Sclerosis (MS) involves a new hypothesis concerning mitochondrial dysfunction, dysregulated lipid metabolism and inflammation. Carnitine palmitoyl transferase 1a (CPT1a) is a key molecule involved in lipid metabolism, which is necessary for transport of lipids into mitochondria. Lipids are important for the central nervous system as it constitute myelin sheaths and thereby shield proteins, e.g. myelin basic protein (MBP), for the immune system. Dysregulated lipid metabolism results in changes in concentration and composition of lipids and down regulates glucose
metabolism, which is the main energy source of the brain. Furthermore, an upregulated lipid metabolism results in prostaglandin E2 (PGE2) production, thereby inducing an inflammatory B and T cell response. It has been found that B cells start generating antibodies to brain proteins after immunization with MBP
suggesting a correlation between MS induction and brain antigens. Blocking CPT1a by Etomoxir favours glucose metabolism rather than lipid metabolism, thus normalizing lipid levels in the brain, as well as downregulating PGE2 production and B cell response. This suggests Etomoxir as an innovative treatment strategy for MS.