Riluzole suppresses experimental autoimmune encephalomyelitis: implications for the treatment of multiple sclerosis.
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.
Gilgun-Sherki
Yossi
Y
Laboratory of Neurosciences, Felsenstein Medical Research Center and Department of Neurology, Rabin Medical Center-Beilinson Campus, The Sackler School of Medicine, Tel Aviv University, Petah Tikva 49100, Israel.
Panet
Hana
H
Melamed
Eldad
E
Offen
Daniel
D
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000188:drug therapy*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019782:Riluzole / Q000627:therapeutic use*; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D013194:Staining and Labeling; D013601:T-Lymphocytes
C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D018696:Neuroprotective Agents; D019782:Riluzole