title: The antioxidant idebenone fails to prevent or attenuate chronic experimental autoimmune encephalomyelitis in the mouse.
abstract: Oxidative stress and mitochondrial dysfunction appear to contribute to neurodegenerative processes during multiple sclerosis (MS). Thus, antioxidants may represent a therapeutic option for MS. The antioxidant idebenone was proven to be beneficial in Friedreich's ataxia and Leber's hereditary optic neuropathy, two disorders caused by mitochondrial alterations. Here we showed that idebenone protected neuronal HT22 cells from glutamate-induced death in vitro. However, in experimental autoimmune encephalomyelitis, idebenone failed to affect disease incidence or onset when applied preventively, or to reduce disease severity when applied therapeutically. Histopathological examination of CNS from idebenone treated mice showed no improvement in inflammation, demyelination, or axonal damage. Thus, we hypothesize that idebenone treatment will likely not benefit patients with MS.
authors.affiliation: Institute for Medical Immunology, Charité-Universitätmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Fiebiger
authors.forename: Helena
authors.initials: H
authors.lastname: Bros
authors.forename: Thomas
authors.initials: T
authors.lastname: Grobosch
authors.forename: Antonia
authors.initials: A
authors.lastname: Janssen
authors.forename: Coralie
authors.initials: C
authors.lastname: Chanvillard
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.forename: Jan
authors.initials: J
authors.lastname: Dörr
authors.forename: Jason M
authors.initials: JM
authors.lastname: Millward
authors.forename: Carmen
authors.initials: C
authors.lastname: Infante-Duarte
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D012720:Severity of Illness Index; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014451:Ubiquinone; C036619:idebenone
keywords: EAE; Idebenone; Inflammation; Multiple sclerosis; Oxidative stress