title: Quetiapine fumarate for the treatment of multiple sclerosis: focus on myelin repair.
abstract: Multiple sclerosis (MS) is a central nervous system disorder that is associated with progressive oligodendrocyte and neuronal loss, axonal degeneration, and demyelination. Several medications that mitigate immune abnormalities reduce both the frequency of relapses and inflammation on magnetic resonance imaging, leading to improved outcomes for people with the relapsing-remitting form of MS. However, there are no treatments for the progressive forms of MS where neurons and axons continue to degenerate; here, neuroprotective therapies, or medications that rebuild myelin to confer axonal well-being, may be useful. Quetiapine fumarate is an atypical antipsychotic with reported remyelinating and neuroprotective properties in inflammatory and noninflammatory models of demyelination, including experimental autoimmune encephalomyelitis, and both cuprizone- and global cerebral ischemia-induced demyelination. Preclinical studies suggest that quetiapine may exert these effects by stimulating proliferation and maturation of oligodendrocytes, releasing neurotrophic factors, increasing antioxidant defences, scavenging for free radicals, and inhibiting activated microglia, astrocytes, and T lymphocytes. Additionally, quetiapine may be beneficial for psychiatric and nonpsychiatric symptoms of MS including depression, anxiety, insomnia, and possibly even pain. These data indicate that clinical trials are justified to determine the safety, tolerability, and efficacy of quetiapine fumarate in MS.
authors.affiliation: Department of Clinical Neurosciences, Faculty of Medicine, Foothills Medical Centre, Calgary MS Clinic, University of Calgary, Calgary, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Zhornitsky
authors.forename: Voon
authors.initials: V
authors.lastname: Wee Yong
authors.forename: Marcus W
authors.initials: MW
authors.lastname: Koch
authors.forename: Aaron
authors.initials: A
authors.lastname: Mackie
authors.forename: Stéphane
authors.initials: S
authors.lastname: Potvin
authors.forename: Scott B
authors.initials: SB
authors.lastname: Patten
authors.forename: Luanne M
authors.initials: LM
authors.lastname: Metz
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003987:Dibenzothiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology; D000069348:Quetiapine Fumarate; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate
keywords: Multiple sclerosis; Neuroprotection; Oligodendrocyte; Quetiapine fumarate; Remyelination