Opioid growth factor (OGF) prevents relapses in mice with relapsing‐remitting EAE, a model for multiple sclerosis

Abstract

Relapse‐remitting multiple sclerosis (MS) is a life‐long, inflammatory disease of the CNS that affects about 350,000 people in the U.S. [Met5]‐enkephalin, termed opioid growth factor (OGF) administered daily to C57BL/6 mice with established chronic progressive experimental autoimmune encephalomyelitis (EAE) reversed the progression of behavioral disease within 6 days of treatment. To determine whether administration of OGF modulates the course of relapsing‐remitting EAE (RR‐EAE) when OGF is administered at the time of induction, female SJL/J mice received proteolipid protein 139–151 emulsified in complete Freund's adjuvant, and were injected daily (i.p.) with OGF (10 mg/kg) or sterile saline. OGF treated RR‐EAE mice had a 40% reduction in peak disease score and significantly fewer relapses over the course of 55 days relative to controls. The duration of relapse for OGF‐treated mice was approximately 1 day in comparison to 13 days for controls. Evaluation of overall disease scores revealed that only 15% of RR‐EAE mice receiving OGF ever expressed disease scores ≥ 4 in comparison to 40% of controls. Histological examination of spinal cords revealed that OGF‐treated mice had markedly less demyelination and fewer activated astrocytes than controls. The results indicate that OGF treatment reduces the progression of RR‐EAE, and may be a novel biological therapy for the treatment of MS. Supported by the Shockey Family Foundation.