Enhanced disease reduction using clozapine, an atypical antipsychotic agent, and glatiramer acetate combination therapy in experimental autoimmune encephalomyelitis.

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dc.contributor.author Green, Laura K en
dc.contributor.author Zareie, Pirooz en
dc.contributor.author Templeton, Nikki en
dc.contributor.author Keyzers, Robert A en
dc.contributor.author Connor, Bronwen en
dc.contributor.author La Flamme, Anne Camille en
dc.date.accessioned 2018-11-07T21:41:14Z en
dc.date.issued 2017-01 en
dc.identifier.issn 2055-2173 en
dc.identifier.uri http://hdl.handle.net/2292/44082 en
dc.description.abstract Atypical antipsychotic agents (AAP) alleviate the symptoms of severe mental health disorders, such as schizophrenia, by antagonizing dopamine and serotonin receptors. Recently, AAP have also been shown to exhibit immunomodulatory properties in the central nervous system (CNS).Building on research which demonstrated the ability of the AAP risperidone and clozapine to modify the disease course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we aimed to more fully investigate the potential of clozapine as a possible treatment for MS.We report that orally administered clozapine significantly reduced the disease severity of EAE in a dose-dependent manner and was effective when administered prophylactically and therapeutically. In comparison to risperidone, quetiapine, and olanzapine, clozapine was the best at reducing disease severity. While clozapine-treated mice had only modest changes to peripheral leukocytes and cytokine responses, these animals had significantly fewer CNS-infiltrating CD4 T cells and myeloid cells. Furthermore, the CNS myeloid cells displayed a less activated phenotype in mice treated with clozapine. Finally, we found that co-administration of clozapine with glatiramer acetate enhanced disease protection compared to either treatment alone.These studies indicate that clozapine is an effective immunomodulatory agent with the potential to treat immune-mediated diseases such as MS. en
dc.format.medium Electronic-eCollection en
dc.language eng en
dc.relation.ispartofseries Multiple sclerosis journal - experimental, translational and clinical en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/2055-2173/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://www.creativecommons.org/licenses/by-nc/3.0/ en
dc.title Enhanced disease reduction using clozapine, an atypical antipsychotic agent, and glatiramer acetate combination therapy in experimental autoimmune encephalomyelitis. en
dc.type Journal Article en
dc.identifier.doi 10.1177/2055217317698724 en
pubs.issue 1 en
pubs.begin-page 2055217317698724 en
pubs.volume 3 en
dc.rights.holder Copyright: The authors en
dc.identifier.pmid 28607752 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 632493 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Pharmacology en
dc.identifier.eissn 2055-2173 en
pubs.record-created-at-source-date 2017-06-13 en
pubs.dimensions-id 28607752 en

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