Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Nat Commun. 2017 Dec 19;8(1):1990. doi: 10.1038/s41467-017-02119-6.

Systematic screening of generic drugs for progressive multiple sclerosis identifies clomipramine as a promising therapeutic.

Author information

1
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
2
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44791, Bochum, Germany.
3
Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB, T6G 2B7, Canada.
4
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada. vyong@ucalgary.ca.

Abstract

The treatment of progressive multiple sclerosis (MS) is unsatisfactory. One reason is that the drivers of disease, which include iron-mediated neurotoxicity, lymphocyte activity, and oxidative stress, are not simultaneously targeted. Here we present a systematic screen to identify generic, orally available medications that target features of progressive MS. Of 249 medications that cross the blood-brain barrier, 35 prevent iron-mediated neurotoxicity in culture. Of these, several antipsychotics and antidepressants strongly reduce T-cell proliferation and oxidative stress. We focus on the antidepressant clomipramine and found that it additionally inhibits B-lymphocyte activity. In mice with experimental autoimmune encephalomyelitis, a model of MS, clomipramine ameliorates clinical signs of acute and chronic phases. Histologically, clomipramine reduces inflammation and microglial activation, and preserves axonal integrity. In summary, we present a systematic approach to identify generic medications for progressive multiple sclerosis with the potential to advance rapidly into clinical trials, and we highlight clomipramine for further development.

PMID:
29259169
PMCID:
PMC5736601
DOI:
10.1038/s41467-017-02119-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center