Treatment of Theiler's virus-induced demyelinating disease with teriflunomide
Francesca Gilli1, Libin Li2,3, Darlene B Royce4
1Department of Neurology, Dartmouth Hitchcock Medical Center (DHMC), Geisel School of Medicine, Lebanon, NH, 03756, USA. francesca.gilli@dartmouth.edu.
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.
Insights
Teriflunomide exhibits anti-inflammatory and antiviral effects in a multiple sclerosis model. While it reduced central nervous system viral load, it did not improve neurological disability or antibody production.
Area of Science:
- Neuroimmunology
- Virology
- Pharmacology
Background:
- Teriflunomide is an oral therapy for relapsing remitting multiple sclerosis (MS).
- Its precise mechanisms of action, including anti-inflammatory and antiviral properties, remain unclear in MS.
- The Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model mimics MS pathology and progressive disability.
Purpose of the Study:
- To investigate the anti-inflammatory and antiviral mechanisms of teriflunomide.
- To evaluate teriflunomide's impact on viral load, immune response, and neurological disability in the TMEV-IDD model.
- To determine the role of central nervous system (CNS) cytokines in teriflunomide's therapeutic effects.
Main Methods:
- Mice were intracranially infected with TMEV to induce the TMEV-IDD model.
- Teriflunomide treatment was administered to assess its effects on CNS viral load.
- Intrathecal immune response and neurological disability progression were monitored throughout the study.
Main Results:
- Teriflunomide demonstrated both anti-inflammatory and antiviral properties within the CNS.
- The treatment did not significantly impact disability progression or intrathecal antibody production in the TMEV-IDD model.
- Observed benefits were primarily mediated by teriflunomide's effects on CNS cytokines.
Conclusions:
- Teriflunomide possesses antiviral activity in the CNS, suggesting potential for treating viral infections.
- Its benefits in the TMEV-IDD model are largely linked to modulation of CNS cytokines.
- Further research is warranted to explore teriflunomide's role as a prophylactic and therapeutic agent for CNS viral infections.
Related Concept Videos
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
01:27Tumor Immunotherapy