Fingolimod and related compounds in a spontaneous autoimmune polyneuropathy.
We investigated potential therapeutic effects of sphingosine-1-phosphate (S1P) receptor modulators FTY720 (fingolimod) and selective S1P1 agonist SEW2871 on a spontaneous autoimmune polyneuropathy (SAP) when given orally at 7 mo (anticipated disease onset) for 4 weeks. Clinical severity, electrophysiologic and histological findings were ameliorated in mice treated with 1 mg/kg of FTY720. Subsequent studies showed that SEW2871 was also effective in halting the progression of SAP, which was accompanied by decreased proliferative and cytokine responses to myelin protein zero (P0), and an increase in regulatory T cells. We conclude that S1P receptor modulators may play a therapeutic role in autoimmune neuropathies.
Kim
Hye-Jung
HJ
Department of Neurology, The University of Chicago, Chicago, IL 60637, United States.
Jung
Cha-Gyun
CG
Dukala
Danuta
D
Bae
Hyun
H
Kakazu
Rafael
R
Wollmann
Robert
R
Soliven
Betty
B
D000818:Animals; D015551:Autoimmunity; D049428:Blood-Nerve Barrier; D015153:Blotting, Western; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D004594:Electrophysiology; D005260:Female; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010069:Oxadiazoles / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011115:Polyneuropathies / Q000188:drug therapy* / Q000276:immunology*; D011409:Propylene Glycols / Q000494:pharmacology*; D012583:Schwann Cells; D012720:Severity of Illness Index; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*
D016207:Cytokines; D007166:Immunosuppressive Agents; D010069:Oxadiazoles; D011409:Propylene Glycols; C503964:SEW2871; D013876:Thiophenes; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine