Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis.

Abstract

Teriflunomide is an orally available anti-inflammatory drug that prevents T and B cell proliferation and function by inhibition of dihydroorotate dehydrogenase. It is currently being developed for the treatment of multiple sclerosis (MS). We report here for the first time the anti-inflammatory effects of teriflunomide in the Dark Agouti rat model of experimental autoimmune encephalomyelitis (EAE). Neurological evaluation demonstrated that prophylactic dosing of teriflunomide at 3 and 10 mg/kg delayed disease onset and reduced maximal and cumulative scores. Therapeutic administration of teriflunomide at doses of 3 or 10 mg/kg at disease onset significantly reduced maximal and cumulative disease scores as compared to vehicle treated rats. Dosing teriflunomide at disease remission, at 3 and 10 mg/kg, reduced the cumulative scores for the remaining course of the disease. Teriflunomide at 10 mg/kg significantly reduced inflammation, demyelination, and axonal loss when dosed prophylactically or therapeutically. In electrophysiological somatosensory evoked potential studies, therapeutic administration of teriflunomide, at the onset of disease, prevented both a decrease in waveform amplitude and an increase in the latency to waveform initiation in EAE animals compared to vehicle. Therapeutic dosing with teriflunomide at disease remission prevented a decrease in evoked potential amplitude, prevented an increase in latency, and enhanced recovery time within the CNS.

• Authors: Jean E Merrill, Susan Hanak, Su-Fen Pu, Jinjun Liang, Chelsea Dang, Deborah Iglesias-Bregna, Brian Harvey, Bin Zhu, Kathleen McMonagle-Strucko
• Journal: Journal of neurology (J Neurol) Vol. 256 Issue 1 Pg. 89-103 (Jan 2009) ISSN: 1432-1459 [Electronic] Germany
• PMID: 19169851 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Central Nervous System Agents
• Crotonates
• Hydroxybutyrates
• Nitriles
• Toluidines
• teriflunomide

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacology)
• Axons (drug effects, pathology)
• Behavior, Animal
• Central Nervous System Agents (administration & dosage, pharmacology)
• Crotonates (administration & dosage, pharmacology)
• Demyelinating Diseases (drug therapy, etiology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Electrophysiology
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, pathology, physiopathology, psychology)
• Evoked Potentials, Somatosensory (drug effects)
• Hydroxybutyrates
• Male
• Nitriles
• Rats
• Toluidines (administration & dosage, pharmacology)
• Treatment Outcome