Immunoregulation of Theiler’s virus-induced demyelinating disease by glatiramer acetate without suppression of antiviral immune responses
While most disease-modifying drugs (DMDs) regulate multiple sclerosis (MS) by suppressing inflammation, they can potentially suppress antiviral immunity, causing progressive multifocal leukoencephalopathy (PML). The DMD glatiramer acetate (GA) has been used for MS patients who are at high risk of PML. We investigated whether GA is safe for use in viral infections by using a model of MS induced by infection with Theiler’s murine encephalomyelitis virus (TMEV). Treatment of TMEV-infected mice with GA neither enhanced viral loads nor suppressed antiviral immune responses, while it resulted in an increase in the Foxp3/Il17a ratio and IL-4/IL-10 production. This is the first study to suggest that GA could be safe for MS patients with a proven viral infection.
We thank Dr. Viromi Fernando and Dr. Eiichiro Kawai for their helpful discussions, and Ms. Sadie Faith Pearson and Ms. Elaine Cliburn Stewart for their excellent technical assistance.
This work was funded by the Teva Neuroscience Investigator-Initiated Program (TNSCOP0049), IDeA from the National Institute of General Medical Science of the NIH (5P30GM110703), KAKENHI from the Japan Society for the Promotion of Science (JP17K15628 and JP16H07356), Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan, and Kindai University Research Enhancement Grant.
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Conflict of interest
The decision to publish this article was solely the responsibility of the authors. All statements, opinions, and content presented in this article are those of the authors and do not represent the opinions of Teva. Teva provided a medical accuracy review of the article.
All experimental procedures involving the use of animals were conducted according to the criteria outlined by the NIH and were approved by the IACUC of Louisiana State University.
- 1.Johnson RT (1998) Chronic inflammatory and demyelinating diseases. In: Johnson RT (ed) Viral infections of the nervous system, 2nd edn. Lippincott-Raven, Philadelphia, pp 227–263Google Scholar
- 4.Sato F, Omura S, Kawai E, Martinez NE, Acharya MM, Reddy PC, Chaitanya GV, Alexander JS, Tsunoda I (2014) Distinct kinetics of viral replication, T cell infiltration, and fibrosis in three phases of myocarditis following Theiler’s virus infection. Cell Immunol 292:85–93CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Plavina T, Subramanyam M, Bloomgren G, Richman S, Pace A, Lee S, Schlain B, Campagnolo D, Belachew S, Ticho B (2014) Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 76:802–812CrossRefPubMedGoogle Scholar