Low Dose Naltrexone Treatment of Established Relapsing-Remitting Experimental Autoimmune EncephalomyelitisLeslie A Hammer, Ian S Zagon and Patricia J McLaughlin*
Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
- *Corresponding Author:
- Patricia J McLaughlin
Department of Neural and Behavioral Sciences
Penn State University College of Medicine
500 University Drive, MC-H109
Hershey, PA 17033-0850, USA
E-mail: [email protected]
Received February 23, 2015; Accepted March 27, 2015; Published April 03, 2015
Citation: Hammer LA, Zagon IS, McLaughlin PJ (2015) Low Dose Naltrexone Treatment of Established Relapsing-Remitting Experimental Autoimmune Encephalomyelitis. J Mult Scler 2:136. doi:10.4172/2376-0389.1000136
Copyright: © 2015 Hammer LA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Relapse-remitting multiple sclerosis is a chronic disorder that affects more than 400,000 individuals in the United States, often reducing their quality of life, increasing medical expenses, and limiting mobility. This study examines modulation of the opioid growth factor (OGF) – OGF receptor (OGFr) axis by low dosages of naltrexone (LDN) as a disease modifying therapy using a mouse model of relapse-remitting experimental autoimmune encephalomyelitis (RR-EAE).
Methods: RR-EAE was induced by immunization of SJL/J mice with proteolipid protein 139-151. After two days of clinical disease, mice were injected intraperitoneally with 0.1 mg/kg naltrexone (LDN) or saline for 40 days. Behavior was observed daily, and periodically, mice were euthanized and spinal cords collected for neuropathological evaluation of glia, T lymphocyte infiltration, and demyelination.
Results: LDN treatment significantly reduced behavioral scores across the 40 day observation period. LDN therapy increased the length of remission, as well as the duration of mild disease. A bimodal distribution of behavioral response to LDN was noted that distinguished “responders” from “non-responders”. Pathological analyses of spinal cord tissue from all LDN-treated mice revealed reductions in the number of inflammatory cells (microglia/macrophages), activated astrocytes, and proliferating cells, as well as decreases in areas of demyelination relative to saline-treated mice with RR-EAE.
Conclusions: These data are the first to demonstrate that modulation of the OGF-OGFr axis by LDN in mice with established RR-EAE is effective at reducing clinical behavior and central nervous system neuropathology.