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

Simon Faissner, Manoj Mishra, Deepak K. Kaushik, Jianxiong Wang, Yan Fan, Claudia Silva, Gail Rauw, Luanne Metz, Marcus Koch and V. Wee Yong ()
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Simon Faissner: University of Calgary
Manoj Mishra: University of Calgary
Deepak K. Kaushik: University of Calgary
Jianxiong Wang: University of Calgary
Yan Fan: University of Calgary
Claudia Silva: University of Calgary
Gail Rauw: Department of Psychiatry, University of Alberta
Luanne Metz: University of Calgary
Marcus Koch: University of Calgary
V. Wee Yong: University of Calgary

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02119-6

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DOI: 10.1038/s41467-017-02119-6

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