Mechanisms of disease: sodium channels and neuroprotection in multiple sclerosis-current status.
Sodium channels can provide a route for a persistent influx of sodium ions into neurons. Over the past decade, it has emerged that sustained sodium influx can, in turn, trigger calcium ion influx, which produces axonal injury in neuroinflammatory disorders such as multiple sclerosis (MS). The development of sodium channel blockers as potential neuroprotectants in MS has proceeded rapidly, and two clinical trials are currently ongoing. The route from the laboratory to the clinic includes some complex turns, however, and a third trial was recently put on hold because of new data that suggested that sodium channel blockers might have multiple, complex actions. This article reviews the development of the concept of sodium channel blockers as neuroprotectants in MS, the path from laboratory to clinic, and the current status of research in this area.
Waxman
Stephen G
SG
Department of Neurology, LCI 707, Yale Medical School, PO Box 20818, New Haven, CT 06520-8018, USA. stephen.waxman@yale.edu
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D026941:Sodium Channel Blockers / Q000627:therapeutic use; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels