FTY720 sustains and restores neuronal function in the DA rat model of MOG-induced experimental autoimmune encephalomyelitis.
FTY720 (fingolimod) is an oral sphingosine 1-phosphate (S1P) receptor modulator under development for the treatment of multiple sclerosis (MS). To elucidate its effects in the central nervous system (CNS), we compared functional parameters of nerve conductance in the DA rat model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) after preventive and therapeutic treatment. We demonstrate that prophylactic therapy protected against the emergence of EAE symptoms, neuropathology, and disturbances to visual and somatosensory evoked potentials (VEP, SEP). Moreover, therapeutic treatment from day 25 to 45 markedly reversed paralysis in established EAE and normalized the electrophysiological responses, correlating with decreased demyelination in the brain and spinal cord. The effectiveness of FTY720 in this model is likely due to several contributing factors. Evidence thus far supports its role in the reduction of inflammation and preservation of blood-brain-barrier integrity. FTY720 may also act via S1P receptors in glial cells to promote endogenous repair mechanisms that complement its immunomodulatory action.
Balatoni
Balázs
B
Novartis Institutes for BioMedical Research, Brunner Strasse 59, A-1235, Vienna, Austria. balazs.balatoni@novartis.com
Storch
Maria K
MK
Swoboda
Eva-M
EM
Schönborn
Vinzenz
V
Koziel
Agnieszka
A
Lambrou
George N
GN
Hiestand
Peter C
PC
Weissert
Robert
R
Foster
Carolyn A
CA
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008137:Longitudinal Studies; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009431:Neural Conduction / Q000187:drug effects; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D007166:Immunosuppressive Agents; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine