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Treatment of Theiler’s virus-induced demyelinating disease with teriflunomide

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Abstract

Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide’s beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler’s encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS. We assessed the effects of the treatment on central nervous system (CNS) viral load, intrathecal immune response, and progressive neurological disability in mice intracranially infected with TMEV. In the TMEV-IDD model, we showed that teriflunomide has both anti-inflammatory and antiviral properties, but there seemed to be no impact on disability progression and intrathecal antibody production. Notably, benefits in TMEV-IDD were mostly mediated by effects on various cytokines produced in the CNS. Perhaps the most interesting result of the study has been teriflunomide’s antiviral activity in the CNS, indicating it may have a role as an antiviral prophylactic and therapeutic compound for CNS viral infections.

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Acknowledgements

This work was supported by research agreements between Sanofi Genzyme and the New Jersey Medical School and Geisel School of Medicine at Dartmouth. The sponsors had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, nor in preparation, and review of the manuscript.

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Authors and Affiliations

  1. Department of Neurology, Dartmouth Hitchcock Medical Center (DHMC), Geisel School of Medicine, Lebanon, NH, 03756, USA

    Francesca Gilli, Darlene B. Royce, Krista D. DiSano & Andrew R. Pachner

  2. Department of Neurology, University of Medicine and Dentistry-New Jersey Medical School, Newark, NJ, USA

    Libin Li & Andrew R. Pachner

  3. GeneScript USA Inc, Piscataway, NJ, USA

    Libin Li

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  1. Francesca Gilli
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  2. Libin Li
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  3. Darlene B. Royce
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  4. Krista D. DiSano
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  5. Andrew R. Pachner
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Correspondence to Francesca Gilli.

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All animal work utilized protocols reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at UMDNJ-New Jersey Medical School and at Dartmouth College.

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The authors declare that they have no conflict of interest.

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Gilli, F., Li, L., Royce, D.B. et al. Treatment of Theiler’s virus-induced demyelinating disease with teriflunomide. J. Neurovirol. 23, 825–838 (2017). https://doi.org/10.1007/s13365-017-0570-8

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  • DOI: https://doi.org/10.1007/s13365-017-0570-8

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