Dartmouth Hitchcock Medical Center

Author Of 1 Presentation

Disease Modifying Therapies – Mechanism of Action Late Breaking Abstracts

LB1278 - Teriflunomide: An Immune Modulating Drug with Antiviral Properties (ID 2177)

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Disease Modifying Therapies – Mechanism of Action



Background: Previously, we evaluated the effect of teriflunomide (TERI) in the Theiler’s encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a model of CNS viral infection and progressive disability in MS. Perhaps the most interesting result of this study was TERI’s antiviral activity in the central nervous system (CNS), indicating it may have a role as an antiviral prophylactic and therapeutic compound for viral infections.


Objective: The current study aimed to extend our previous work by focusing on the antiviral effect of TERI to test the hypothesis that TERI would be beneficial for treating viral infections, especially in MS patients with an elevated risk of a subclinical viral reactivation and/or reinfection events. We also reassessed the impact of TERI on disability progression and intrathecal synthesis of immunoglobulins (Igs) by using a more efficient model system.


Methods: TMEV-IDD was induced by intracerebral injection of Theiler's virus into SJL mice. Ninety-two mice were included: 28 sham controls, 32 TMEV-IDD mice treated with TERI, and 32 TMEV-IDD mice treated with vehicle only. Mice were monitored for neurological impairment by using the Rotarod test and an automated HomeCage analysis (HCA) system. The measures used were Luminex analysis for CSF and serum anti-TMEV antibody (BAbs) and real-time PCR of both brain and spinal RNA for TMEV RNA and IgG1 mRNA. Mice were necropsied at 120 days post-infection, i.e., at the chronic stage of the disease.


Results: at necropsy, 27% of the infected mice had cleared the virus, as PCR for TMEV RNA in spinal cords and brains was negative. Overall, the rate of viral clearance was higher in the TERI- vs. vehicle-treated group (42% vs. 12%; p=0.04). Viral load was slightly lower in the TERI- vs. vehicle-treated animals, but the difference was not statistically significant (p=0.10). The serum and CSF BAbs levels were lower in TERI- vs. vehicle-treated mice (p≤0.041). Levels of IgG1 mRNA within the CNS parenchyma were increased in infected mice compared to sham controls (all p£0.018). No difference in brain IgG1 mRNA was observed in TERI- vs. vehicle-treated mice (p>0.61), but IgG1 mRNA levels in the spinal cord were lower in the TERI-treated group (p<0.06). There was no difference comparing disability progression as tested by Rotarod in TERI vs. vehicle-treated mice (p>0.51). Similarly, the digital activity data from the HCA showed a reduction in the locomotor activity, i.e., distances traveled by the mice throughout the recording, of TMEV-IDD animals relative to sham control mice, without a significant difference in this measure between TERI- and vehicle-treated animals.


Conclusions: present findings confirm our previously published results: in the TMEV-IDD model, TERI treatment shows both anti-inflammatory and antiviral properties, without any significant impact on disability progression.