PIOGLITAZONE IS SUPERIOR TO QUETIAPINE, CLOZAPINE AND TAMOXIFEN AT ALLEVIATING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Abstract

Recent evidence suggests that clozapine, quetiapine, tamoxifen and pioglitazone may improve functional recovery in multiple sclerosis (MS). We have compared the effectiveness of oral administration of these drugs, beginning at peak disease, at reducing disease severity and demyelination in mice subjected to experimental autoimmune encephalomyelitis (EAE). Unlike clozapine, quetiapine and tamoxifen, administration of pioglitazone beginning at peak disease decreased clinical scores and lumbar white matter loss in EAE mice. Using kinematic gait analysis, we found that pioglitazone also maintained normal movement of the hip, knee and ankle joints for 44 days after EAE induction. This long-lasting preservation of hindleg joint movements was accompanied by reduced white matter loss, microglial and macrophage activation and the expression of pro-inflammatory genes in the lumbar spinal cord of EAE mice. These results support clinical findings that suggest pioglitazone may reduce the loss of motor function in MS by decreasing inflammation and myelin damage.