title: Sphingosine 1-phosphate receptor modulator fingolimod (FTY720) does not promote remyelination in vivo.
abstract: The sphingosine 1-phosphate (S1P) receptor modulators have emerged as a new therapeutic opportunity paradigm for the treatment of immune-mediated demyelinating diseases such as multiple sclerosis (MS). The S1P analog fingolimod (FTY720) has been shown to alleviate disease burden in immune-mediated animal models of MS, and has been approved for treatment in clinical trials in patients with MS in the United States. While the immunological effects of FTY720 are well established, there is controversy in the literature regarding the contribution of FTY720 on myelin repair. Here, we directly assessed the impact of FTY720 on myelin repair in cuprizone and lysolecithin (LPC) demyelination models that have a minimal immunological component. FTY720 failed to promote remyelination in either animal model. These studies suggest that while FTY720 may be effective at modulating the immunological attack in MS, it may benefit from an add-on therapy to enhance the myelin repair required for long-term functional restoration in MS.
authors: Biogen Idec Inc, Neuro-Discovery Biology, 14 Cambridge Center, Cambridge, Massachusetts 02142, United States.
authors: Yinghui
authors: Y
authors: Hu
authors: Xinhua
authors: X
authors: Lee
authors: Benxiu
authors: B
authors: Ji
authors: Kevin
authors: K
authors: Guckian
authors: Daniel
authors: D
authors: Apicco
authors: R Blake
authors: RB
authors: Pepinsky
authors: Robert H
authors: RH
authors: Miller
authors: Sha
authors: S
authors: Mi
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D003471:Cuprizone / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000188:drug therapy; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects*; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002614:Chelating Agents; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D003471:Cuprizone; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine