Dimethyl fumarate as a promising therapeutic candidate for virus-associated myelopathy

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neuroinflammatory disease with no effective treatment. In this study, we investigated whether dimethyl fumarate (DMF), an immunomodulatory agent approved for treating multiple sclerosis, exerts therapeutic effects relevant to HAM/TSP. Peripheral blood mononuclear cells (PBMCs) from 16 people living with HAM/TSP were used to evaluate the effects of DMF on cell viability, spontaneous proliferation, inflammatory cytokine production and HTLV-1 proviral load (PVL). DMF significantly inhibited lymphocyte proliferation in a concentration-dependent manner, with reductions of 42.1% at 10 µM, 56.3% at 25 µM, 60.6% at 50 µM and 69.9% at 100 µM. This suppressive effect was particularly evident in CD8+ T cells, CD4+ T cells and HTLV-1-infected CD4+ T cells. Furthermore, DMF reduced the production of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) released from these proliferating cells. A reduction in PVL was also observed in a subset of ex vivo PBMC cultures derived from individuals with HAM/TSP exhibiting high viral proliferative activity. These results suggest that DMF suppresses pathogenic immune activation in HAM/TSP and may therefore represent a promising therapeutic candidate for this disabling neuroinflammatory disorder.