The combined treatment of Copaxone and Salirasib attenuates experimental autoimmune encephalomyelitis (EAE) in mice.
EAE is a common animal model for multiple sclerosis (MS). Immunomodulatory treatments such as glatiramer acetate (GA, Copaxone) are beneficial in EAE but are not universally effective in the clinic. The Ras inhibitor farnesylthiosalycylic acid (FTS, Salirasib), efficiently ameliorate EAE as well. Here we demonstrate a synergistic beneficial effect of the combined GA and FTS treatment on EAE; 22.5% of the combined-treatment mice developed disease compared to 87.5%, 77.5% and 82.5% of mice treated with vehicle, GA and FTS, respectively, results supported by MRI, histological, immunological and biochemical data. Such a combined treatment may improve clinical outcome in MS patients.
Aizman
Elizabeta
E
Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Mor
Adi
A
Chapman
Joab
J
Assaf
Yaniv
Y
Kloog
Yoel
Y
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004265:DNA Helicases; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005204:Farnesol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017254:Leukemic Infiltration / Q000188:drug therapy / Q000209:etiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000627:therapeutic use*; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012459:Salicylates / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013154:Spleen / Q000166:cytology; D018709:Statistics, Nonparametric; D013997:Time Factors
D017252:CD3 Complex; D002352:Carrier Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D010455:Peptides; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol; D000068717:Glatiramer Acetate; D048049:Extracellular Signal-Regulated MAP Kinases; D004265:DNA Helicases; C492055:G3bp1 protein, mouse; D020365:RNA Helicases