Sphingosine 1-phosphate receptor modulator fingolimod (FTY720) does not promote remyelination in vivo
| Autor: | Daniel J. Apicco, Yinghui Hu, Sha Mi, Xinhua Lee, Kevin Guckian, R. Blake Pepinsky, Benxiu Ji, Robert H. Miller |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Biology
Rats Sprague-Dawley Cellular and Molecular Neuroscience Myelin chemistry.chemical_compound Cuprizone Mice In vivo Sphingosine hemic and lymphatic diseases Fingolimod Hydrochloride medicine Animals Humans Remyelination Molecular Biology Myelin Sheath Chelating Agents Multiple sclerosis Cell Biology medicine.disease Fingolimod Oligodendrocyte Nerve Regeneration Rats Mice Inbred C57BL Disease Models Animal Receptors Lysosphingolipid medicine.anatomical_structure chemistry Propylene Glycols Immunology Immunosuppressive Agents medicine.drug Demyelinating Diseases |
| Zdroj: | Molecular and cellular neurosciences. 48(1) |
| ISSN: | 1095-9327 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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