TY - CONF
T1 - Comparison of Etomoxir, a lipid metabolism blocker, and interferon-β treatment on antibody recognition of brain proteins in Multiple Sclerosis
AU - Mørkholt, Anne Skøttrup
AU - Kastaniegaard, Kenneth
AU - Trabjerg, Michael Sloth
AU - Niganze, Wanda
AU - Gopalasingam, Gopana
AU - Larsen, Agnete
AU - Stensballe, Allan
AU - Nielsen, Søren
AU - Nieland, John Dirk
PY - 2017
Y1 - 2017
N2 - 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 glucosemetabolism, 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 MBPsuggesting 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.
AB - 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 glucosemetabolism, 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 MBPsuggesting 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.
KW - Multiple sclerosis
KW - Lipid Metabolism
KW - Experimental autoimmune encephalomyelitis, EAE
M3 - Poster
T2 - Annual Meeting of the Consortium of Multiple Sclerosis Centers, CMSC
Y2 - 24 May 2017 through 27 May 2017
ER -