Teriflunomide is a once-daily oral immunomodulatory agent recently approved in the United States for the treatment of relapsing
multiple sclerosis (RMS). This study investigated neurophysiological deficits in descending spinal cord motor tracts during
experimental autoimmune encephalomyelitis (EAE; a model of
multiple sclerosis) and the functional effectiveness of prophylactic or therapeutic
teriflunomide treatment in preventing the debilitating
paralysis observed in this model. Relapsing-remitting EAE was induced in Dark Agouti rats using rat spinal cord homogenate. Animals were treated with oral
teriflunomide (10 mg/kg daily) prophylactically, therapeutically, or with vehicle (control). Transcranial magnetic motor-evoked potentials were measured throughout the disease to provide quantitative assessment of the neurophysiological status of descending motor tracts. Axonal damage was quantified histologically by
silver staining. Both prophylactic and therapeutic
teriflunomide treatment significantly reduced maximum EAE disease scores (P < 0.0001 and P = 0.0001, respectively) compared with vehicle-treated rats. Electrophysiological recordings demonstrated that both
teriflunomide treatment regimens prevented a delay in wave-form latency and a decrease in wave-form amplitude compared with that observed in vehicle-treated animals. A significant reduction in axonal loss was observed with both
teriflunomide treatment regimens compared with vehicle (P < 0.0001 and P = 0.0014, respectively). The results of this study suggest that therapeutic
teriflunomide can prevent the deficits observed in this animal model in descending spinal cord motor tracts. The mechanism behind reduced axonal loss and improved motor function may be primarily the reduced
inflammation and consequent
demyelination observed in these animals through the known effects of
teriflunomide on impairing proliferation of stimulated T cells. These findings may have significant implications for patients with RMS.