Inhibition of Ras attenuates the course of experimental autoimmune neuritis.

Abstract

EAN induced in Lewis rats by immunization with peripheral bovine myelin was treated by the Ras inhibitor farnesylthiosalicylate (FTS). Treatment from day 0 with FTS (5 mg/kg intraperitoneally twice daily) attenuated peak clinical scores (mean+/-S.E., 2.5+/-0.5 compared to 4.1+/-0.5 in saline treated controls, p=0.018, t-test) but not recovery. Treatment from day 10 with FTS attenuated peak disability (2.5+/-0.6, p=0.032 compared to saline treated controls) and improved recovery (0.84+/-0.42, untreated controls 2.4+/-0.6, p=0.028 by repeated measures ANOVA). Effects were confirmed by rotarod and nerve conduction studies. An inactive analogue, geranylthiosalicylate, had no clinical effect. Inhibition of Ras is of potential use in the treatment of inflammatory neuropathies.