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Endogenous Opioids and the Treatment of Multiple Sclerosis | 45952

神経学および神経生理学ジャーナル

ISSN - 2155-9562

概要

Endogenous Opioids and the Treatment of Multiple Sclerosis

Ian S. Zagon and Patricia J. McLaughlin

Multiple sclerosis is an autoimmune disorder of the central nervous system that affects approximately 400,000
people in the United States and 2 million individuals worldwide. The disease is chronic, often progressive, and
manifests through proliferation and activation of T-lymphocytes and astrocytes, resulting in demyelination and
axonal damage. Approved therapies are interferon-based or involve T-cell immune modulators; however, many
treatments have unacceptable side-effects, are cost-prohibitive, and/or require clinical visits for administration. There
is an unmet need for disease-modifying therapies that are non-toxic and readily available. The regulatory pathway
involving opioid growth factor (OGF) and its nuclear-associated receptor, OGFr, is involved in several autoimmune
diseases including multiple sclerosis. The OGF-OGFr axis appears to be aberrant in that patients with autoimmune
disorders often have reduced levels of peptide, an inhibitory growth factor targeting cell proliferation.OGF is an
endogenous neuropeptide, chemically termed [Met5]-enkephalin, that ameliorates the course of experimental
autoimmune encephalomyelitis when treatment is initiated at the time of induction in mouse models of progressive
disease. OGF therapy initiated at the time of disease presentation reversed progressive disease within one week.
OGF treatment of the mouse model of relapse-remitting experimental autoimmune encephalomyelitis resulted in a
significant reduction in the severity and number of relapses. Treatment with OGF of established relapse-remitting
disease diminished peak clinical disease and suppressed relapses. Preclinical studies, as well as clinical
observations, support the use of endogenous opioids as safe and effective disease-modifying biotherapeutics.