Abstract | BACKGROUND: METHODS: The effect of FTY720 was assessed in relapsing-progressive EAE in mice. RESULTS: Early intervention during relapsing EAE could completely inhibit subsequent relapses, inhibited the accumulation of neurodegeneration, and facilitated motor recovery. However, when examined in secondary progressive EAE, that develops after the accumulation of deficit from relapsing disease, long-term treatment with FTY720 failed to slow deterioration when initiated late (4 months) into the disease course. CONCLUSIONS: This study indicates that early intervention with immunosuppressive agents may inhibit the generation of the neurodegenerative microenvironment, which is no longer responsive to potent immunosuppression. However, if treatment is initiated too late, progressive, neurological-disease continues unabated. This suggests that immunosuppression is insufficient to control secondary progression in animals, as has been found so far to be the case in MS, and may warrant early intervention with FTY720 for optimal treatment benefit.
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Authors | Sarah Al-Izki, Gareth Pryce, Samuel J Jackson, Gavin Giovannoni, David Baker |
Journal | Multiple sclerosis (Houndmills, Basingstoke, England)
(Mult Scler)
Vol. 17
Issue 8
Pg. 939-48
(Aug 2011)
ISSN: 1477-0970 [Electronic] England |
PMID | 21459808
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunosuppressive Agents
- Propylene Glycols
- Fingolimod Hydrochloride
- Sphingosine
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Topics |
- Animals
- Disease Progression
- Encephalomyelitis, Autoimmune, Experimental
(drug therapy, pathology)
- Female
- Fingolimod Hydrochloride
- Immunosuppressive Agents
(therapeutic use)
- Male
- Mice
- Nerve Degeneration
(drug therapy)
- Propylene Glycols
(therapeutic use)
- Recovery of Function
(drug effects)
- Sphingosine
(analogs & derivatives, therapeutic use)
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