Aubagio® (teriflunomide), an immunomodulatory drug, could become a potential novel treatment for patients with myasthenia gravis (MG), according to a study recently published in Cellular and Molecular Neurobiology.

“The data presented herein suggest that teriflunomide may be a suitable candidate for use in MG patients and even in chronic inflammatory neuromuscular diseases owing to its widespread effect on the immune system and its low side effects,” the authors wrote.

This experimental study divided mice into 3 groups. Cohort 1 had a total of 21 mice, which received immunization with acetylcholine receptor (AChR) for 3 doses to mimic MG. Then, the researchers administered teriflunomide 10 mg/kg/day, with an intraperitoneal injection, while continuing the immunizations. Group 2 consisted of 19 mice and only received the AChR vaccine. Finally, group 3 was made up of 10 control mice, who only received a mock immunization.

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The researchers observed an overall decrease in the CD4 T cell count and lower interferon-gamma (IFN-γ), interleukin (IL)-2, IL-17A, IL-22, and granulocyte-macrophage colony-stimulating factor in both the lymph nodes and spleen. The thymus also showcased lower CD4 T cells.

Regarding B cells, plasma cells marked with CD19, CD138, and lambda also reduced their overall count, while the CD138 marker further showcased less fluorescent intensity. The results suggest that the absolute number of immunoglobulin G (IgG) secreting plasma cells also decreased.

Finally, plasma anti-AChR-specific autoantibody levels experienced selective changes. A possible explanation is that teriflunomide could mediate the IgG antibody isotype processing.

Teriflunomide, and its prodrug, leflunomide, are irreversible inhibitors of the mitochondrial enzyme dihydroorotate dehydrogenase, consequently impairing the pyrimidine de novo synthesis and reducing B and T cell quantities. Both drugs are already part of the therapeutic options for rheumatoid arthritis.

“In conclusion, our study shows that teriflunomide has clinical benefits and prevented the progression of the disease in a murine model of MG through different possible mechanisms, including suppression of immune responses by reducing the number of cytokine-producing T cells by changing the functions of plasma cells and by leading selective changes in anti-AChR antibody quantities and types,” the authors wrote.

Reference

Koseoglu E, Sungur N, Muhtaroglu S, Zararsiz G, Eken A. The beneficial clinical effects of teriflunomide in experimental autoimmune myasthenia gravis and the investigation of the possible immunological mechanisms. Cell Mol Neurobiol. Published online October 11, 2022. doi:10.1007/s10571-022-01286-5