Complement inhibitor prevents disruption of sodium channel clusters in a rabbit model of Guillain-Barré syndrome

J Neuroimmunol. 2008 Dec 15;205(1-2):101-4. doi: 10.1016/j.jneuroim.2008.09.016. Epub 2008 Oct 29.

Abstract

Complement-mediated disruption of voltage-gated sodium channels at the nodes of Ranvier acts in the development of acute motor axonal neuropathy. Nafamostat mesilate, a synthetic serine protease inhibitor, used in clinical practice for more than 20 years, has anti-complement activity. Acute motor axonal neuropathy rabbits obtained by GM1 ganglioside sensitization were or were not given nafamostat mesilate intravenously. Complement deposition and sodium channel disruption in the spinal anterior roots were significantly less frequent in the treated rabbits than in the controls. Nafamostat mesilate inhibited complement deposition and prevented sodium channel disruption. This provided the rationale for a clinical trial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamidines
  • Complement C3 / metabolism
  • Complement Inactivating Agents / pharmacology*
  • Complement Inactivating Agents / therapeutic use
  • Disease Models, Animal
  • Guanidines / pharmacology*
  • Guanidines / therapeutic use
  • Guillain-Barre Syndrome / drug therapy
  • Guillain-Barre Syndrome / pathology*
  • Guillain-Barre Syndrome / physiopathology
  • Infusion Pumps, Implantable
  • Rabbits
  • Random Allocation
  • Ranvier's Nodes / drug effects*
  • Ranvier's Nodes / metabolism
  • Sodium Channels / metabolism*

Substances

  • Benzamidines
  • Complement C3
  • Complement Inactivating Agents
  • Guanidines
  • Sodium Channels
  • nafamostat