Contributions
Abstract: EP1606
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: Human T-lymphotropic virus (HTLV)-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare chronic progressive myelopathy with no approved therapies. Peripheral blood mononuclear cells (PBMCs) from patients with HAM/TSP demonstrate spontaneous lymphoproliferation in short-term culture without exogenous stimulators.
Objective: 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 MS, can reduce spontaneous proliferation of PBMCs from patients with HAM/TSP ex vivo.
Methods: 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) expression before and after PBMC culture, with and without teriflunomide.
Results: In culture, teriflunomide did not affect cell viability. A dose-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 expression in these short-term cultures.
Conclusions: Ex vivo, teriflunomide reduced spontaneous lymphoproliferation of PBMCs, specifically CD8+ T cells, from patients with HAM/TSP, without changing proviral load or tax mRNA expression. These results suggest that teriflunomide inhibits abnormal T-cell proliferation associated with HTLV-1 infection. Further studies are needed to assess possible long-term effects of teriflunomide in HTLV-1-associated neurological disease.
Disclosure: YA: Nothing to disclose. NN: Nothing to disclose. JO: Nothing to disclose. MM: Former employee of Sanofi. JC: Employee of Sanofi with ownership interest. TJT: Employee of Sanofi with ownership interest. SJ: Nothing to disclose.
Study supported by Sanofi.
Abstract: EP1606
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: Human T-lymphotropic virus (HTLV)-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare chronic progressive myelopathy with no approved therapies. Peripheral blood mononuclear cells (PBMCs) from patients with HAM/TSP demonstrate spontaneous lymphoproliferation in short-term culture without exogenous stimulators.
Objective: 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 MS, can reduce spontaneous proliferation of PBMCs from patients with HAM/TSP ex vivo.
Methods: 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) expression before and after PBMC culture, with and without teriflunomide.
Results: In culture, teriflunomide did not affect cell viability. A dose-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 expression in these short-term cultures.
Conclusions: Ex vivo, teriflunomide reduced spontaneous lymphoproliferation of PBMCs, specifically CD8+ T cells, from patients with HAM/TSP, without changing proviral load or tax mRNA expression. These results suggest that teriflunomide inhibits abnormal T-cell proliferation associated with HTLV-1 infection. Further studies are needed to assess possible long-term effects of teriflunomide in HTLV-1-associated neurological disease.
Disclosure: YA: Nothing to disclose. NN: Nothing to disclose. JO: Nothing to disclose. MM: Former employee of Sanofi. JC: Employee of Sanofi with ownership interest. TJT: Employee of Sanofi with ownership interest. SJ: Nothing to disclose.
Study supported by Sanofi.