Inhibition of Ras attenuates the course of experimental autoimmune neuritis.
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.
Kafri
Michal
M
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Kloog
Yoel
Y
Korczyn
Amos D
AD
Ferdman-Aronovich
Ramona
R
Drory
Vivian
V
Katzav
Aviva
A
Wirguin
Itzhak
I
Chapman
Joab
J
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004347:Drug Interactions; D004576:Electromyography / Q000379:methods; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005204:Farnesol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009169:Mycobacterium tuberculosis; D009185:Myelin Proteins; D009431:Neural Conduction / Q000187:drug effects; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D045442:Rotarod Performance Test / Q000379:methods; D012459:Salicylates / Q000008:administration & dosage*; D012720:Severity of Illness Index; D018631:ras Proteins / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D009185:Myelin Proteins; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D003208:Concanavalin A; D005204:Farnesol; D018631:ras Proteins