To explore whether teriflunomide, a dihydroorotate dehydrogenase inhibitor that reduces the proliferation of activated lymphocytes and is approved for the treatment of relapsing forms of multiple sclerosis (MS), can reduce spontaneous proliferation of peripheral blood mononuclear cells (PBMCs) from patients with human T-lymphotropic virus (HTLV)-1-associated myelophathy/tropical spastic paraparesis (HAM/TSP) ex vivo.

HAM/TSP is a rare chronic progressive myelopathy with no approved therapies. PBMCs from patients with HAM/TSP demonstrate spontaneous lymphoproliferation in short-term culture without exogenous stimulators.

PBMCs from patients with HAM/TSP were grown in culture with 0, 25, 50, or 100 μM teriflunomide. Lymphocyte proliferation was measured at Days 3 to 5 using tritiated thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester dye dilution assays. Digital droplet polymerase chain reaction was used to measure HTLV-1 proviral load and tax (HTLV-1 transcription factor) messenger RNA (mRNA)/Tax protein expression before and after PBMC culture, with and without teriflunomide.

In culture, teriflunomide did not affect cell viability. A concentration-dependent reduction in spontaneous proliferation of PBMCs (specifically CD8+ T cells) was observed with 25 (30% inhibition), 50 (45% inhibition), and 100 μM (80% inhibition) of teriflunomide. There was no change in HTLV-1 proviral load or tax mRNA/Tax protein expression in these short-term cultures.

Ex vivo, teriflunomide reduced spontaneous lymphoproliferation of PBMCs, specifically CD8+ T cells, from patients with HAM/TSP, with no significant change in HTLV-1 proviral load or tax mRNA/Tax protein expression. These results suggest that teriflunomide inhibits abnormal T-cell proliferation associated with HTLV-1 infection. Further clinical studies are ongoing to assess possible long-term effects of teriflunomide in HTLV-1–associated neurological disease.