title: Targeting synaptic pathology in multiple sclerosis: fingolimod to the rescue?
abstract: Multiple sclerosis (MS) is an inflammatory disorder affecting the brain and spinal cord. Major hallmarks of MS typically include inflammation, demyelination and axon degeneration, although recent studies have also implicated synaptic dysfunction and degeneration in disease pathogenesis. The discovery that treatment with the orally active immunomodulatory drug fingolimod (FTY720) confers benefits in animal models and human patients has opened up new avenues for the treatment of MS. In the present issue of the BJP, Rossi and colleagues used a mouse model of MS [experimental autoimmune encephalomyelitis (EAE)] to provide new evidence suggesting that fingolimod may target MS symptoms, at least in part, by ameliorating synaptic dysfunction. They demonstrated that fingolimod reversed modifications in glutamatergic transmission found in the striatum of EAE mice, accompanied by a reduction in the severity of dendritic spine loss. This report suggests that fingolimod treatment can have beneficial effects on synaptic pathology in MS, raising the intriguing possibility that fingolimod treatment may also be advantageous in other diseases of the nervous system where inflammation and synaptic pathology contribute to disease pathogenesis. LINKED ARTICLE This article is a commentary on Rossi et al., pp. 861-869 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01579.x.
authors.affiliation: School of Biomedical Sciences, College of Medicine & Veterinary Medicine, University of Edinburgh, Edinburgh, UK. t.gillingwater@ed.ac.uk
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Gillingwater
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology*; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine