Low dose naltrexone inhibits the progression of clinical disease in established relapse‐remitting experimental autoimmune encephalomyelitis ő a model for multiple sclerosis (651.3)

Abstract

Relapse‐remitting multiple sclerosis (RR‐MS) is a chronic disorder involving inflammatory attacks on the CNS. RR‐MS affects about 350,000 people in the U.S. significantly reducing the quality of life. The Opioid Growth Factor (OGF)‐Opioid Growth Factor Receptor (OGFr) pathway has been reported to be involved in experimental autoimmune encephalomyelitis (EAE). Blockade of OGF‐OGFr interaction using low dosages of the opioid antagonist naltrexone (LDN) alters the course of disease. SJL/J mice were immunized with PLP139‐151, and were injected (ip) daily with 0.1 mg/kg naltrexone or saline beginning 2 days after initial signs of disease. Within 9 days of LDN treatment mice had markedly reduced mean behavioral scores compared to controls, with the sum of behavioral scores being 142.9±11.5 for the RR‐EAE+Saline group in comparison to 78.8±9.1for the RR‐EAE+LDN group. In the LDN group, 80% of the mice had complete remission (behavioral scores of 0.5 or less) during the 40 day observation period. Moreover, LDN‐treated mice demonstrated a 4‐fold increase in mild disease scores relative to controls. The results indicate that modulation of the OGF‐OGFr pathway by LDN in established RR‐EAE inhibited the severity of initial flair and limited the progression of clinical disease, with many LDN‐treated mice showing complete remission. These observations support LDN as a non‐toxic/safe biotherapy for the treatment of RR‐MS.Grant Funding Source: Shockey Family Foundation