Glutamate inhibition in MS: the neuroprotective properties of riluzole.
In addition to demyelination and damage to oligodendrocytes, axonal injury and neuronal cell death are dominating histopathological characteristics of multiple sclerosis (MS). Still little is known about the cause of the damage. Extracellular accumulation of glutamate contributes to excitotoxic injury of neurons and glial cells, suggesting that the maintenance of subtoxic extracellular glutamate levels may be crucial. Riluzole is a neuroprotective agent that inhibits the release of glutamate from nerve terminals and modulates glutamate, i.e., kainate and NMDA receptors. It inhibits excitotoxic injury in several experimental models of neurodegenerative disease. We performed a small run-in versus treatment MR-monitored pilot study in 16 primary progressive MS patients. The results suggest that riluzole reduces the rate of cervical cord atrophy and the development of T1 hypointense lesions on magnetic resonance imaging in primary progressive MS. The rate of brain atrophy was only slightly decreased. The results indicate an effect on mechanisms involving lesion evolution and axonal loss, but no clear effect on new lesion formation. However, the data suffer from several limitations and must be confirmed in future trials.
Killestein
Joep
J
Department of Neurology, VU Medical Centre, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. J.Killestein@vumc.nl
Kalkers
Nynke F
NF
Polman
Chris H
CH
D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019782:Riluzole / Q000627:therapeutic use*; D013116:Spinal Cord / Q000473:pathology
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D019782:Riluzole