Riluzole suppresses experimental autoimmune encephalomyelitis: implications for the treatment of multiple sclerosis

Brain Res. 2003 Nov 7;989(2):196-204. doi: 10.1016/s0006-8993(03)03343-2.

Abstract

Recent studies suggest that glutamate neurotoxicity is involved in the pathogenesis of multiple sclerosis (MS), and that treatment with glutamate receptor (AMPA/kainate) antagonists inhibits experimental autoimmune encephalomyelitis (EAE), the conventional model of MS. Therefore, we examined whether riluzole, an inhibitor of glutamate transmission, affects the pathogenesis and clinical features of MS-like disease in myelin oligodendrocyte glycoprotein (MOG)-induced EAE in mice. Here we report that riluzole (10 mg/kgx2/day, i.p.), administered before and even after the appearance of clinical symptoms, dramatically reduced the clinical severity of MOG-induced EAE, while all the MOG-immunized control mice developed significant clinical manifestations. Moreover, the riluzole-treated mice demonstrated only mild focal inflammation, and less demyelination, compared to MOG-treated mice, using histological methods. Furthermore, riluzole markedly reduced axonal disruption, as assessed by Bielshowesky's silver staining and by antibodies against non-phosphorylated neurofilaments (SMI-32). No difference was detected in the immune system potency, as T-cell proliferative responses to MOG were similar in both groups. In conclusion, our study demonstrates, for the first time, that riluzole can reduce inflammation, demyelination and axonal damage in the CNS and attenuate the clinical severity of MOG-induced EAE. These results suggest that riluzole, a drug used in amyotrophic lateral sclerosis (ALS), might be beneficial for the treatment of MS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Female
  • Immunohistochemistry
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Multiple Sclerosis / drug therapy*
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / pharmacology
  • Myelin-Oligodendrocyte Glycoprotein
  • Neurologic Examination
  • Neuroprotective Agents / therapeutic use*
  • Riluzole / therapeutic use*
  • Spinal Cord / anatomy & histology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Staining and Labeling
  • T-Lymphocytes

Substances

  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Neuroprotective Agents
  • Riluzole