title: Fumaric acid and its esters: an emerging treatment for multiple sclerosis with antioxidative mechanism of action.
abstract: Fumaric acid was originally therapeutically used in psoriasis. Several lines of evidence have demonstrated immunomodulatory but also neuroprotective effects for FAE. Clinical studies in psoriasis showed a reduction of peripheral CD4+ and CD8+ T-lymphocytes due to the ability of FAE to induce apoptosis. In vitro studies with the ester dimethylfumarate (DMF) described an inhibitory effect on nuclear factor kappa B (NF-κB)-dependent transcription of tumor necrosis factor-alpha (TNF-α) induced genes in human endothelial cells. Animal experiments in the mouse model of central nervous system demyelination, MOG-induced experimental autoimmune encephalomyelitis, revealed a clear preservation of myelin and axonal density in the plaque. Molecular studies showed that this is based on the antioxidative mechanism of action via induction of the transcription factor Nrf-2. A phase II clinical trial in relapsing-remitting multiple sclerosis (RRMS) patients with dimethylfumarate showed a significant reduction in the number of gadolinium enhancing lesions after 24weeks.
authors.affiliation: Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany. ralf.gold@rub.de
authors.forename: R
authors.initials: R
authors.lastname: Gold
authors.forename: R A
authors.initials: RA
authors.lastname: Linker
authors.forename: M
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D005650:Fumarates / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology
chemical_list: D005650:Fumarates; D007166:Immunosuppressive Agents; C032005:fumaric acid