Estrogen receptor- ligand treatment after disease onset is neuroprotective in the multiple sclerosis model

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and neurodegeneration. Current MS treatments were designed to reduce inflammation in MS rather than directly to prevent neurodegeneration. Estrogen has well-documented neuroprotective effects in a variety of disorders of the CNS, including experimental autoimmune encephalomyelitis (EAE), the most widely used mouse model of MS. Treatment with an estrogen receptor- (ER) ligand is known to ameliorate clinical disease effectively and provide neuroprotection in EAE. However, the protective effects of this ER ligand have been demonstrated only when administered prior to disease (prophylactically). Here we tested whether ER ligand treatment could provide clinical protection when treatment was initiated after onset of disease (therapeutically). We found that therapeutic treatment effectively ameliorated clinical disease in EAE. Specifically, ER ligand-treated animals exhibited preserved axons and myelin compared with vehicle-treated animals. We observed no difference in the number of T lymphocytes, macrophages, or microglia in the CNS of vehicle- vs. ER ligand-treated animals. Our findings show that therapeutically administered ER ligand successfully treats clinical EAE, bearing translational relevance to MS as a candidate neuroprotective agent. (c) 2013 Wiley Periodicals, Inc.