Safinamide and flecainide protect axons and reduce microglial activation in models of MS


It is known that axonal degeneration is a major cause of permanent disability in MS. Sodium channel blocking agents have been shown to protect white matter axons against degeneration in experimental models of MS, though it is not yet certain if this protection is due to a direct effect on axons or occurs indirectly via immune modulation. This research group examined the ability of the sodium channel blocking agents Safinamide and Flecainide to protect white matter axons in two forms of experimental autoimmune encephalomyelitis (EAE), a common model of MS.

Safinamide provided significant protection against neurological deficit and axonal degeneration in EAE, even when administration was delayed until after the onset of neurological deficit. There was a significant reduction in the activation of microglia/macrophages within the CNS. Flecainide was also potent in suppressing microglial activation in EAE. To see if the suppression of microglia was an indirect effect of the reduction on axonal damage, or was due to a direct effect of Safinamide on microglial cells, the in vitro action of Safinamide in cultured primary rat microglial cells was examined. Safinamide decreased microglial superoxide production and enhanced the production of the anti-gluthione, indicating that suppression of microglia is a direct effect.

This demonstrates that safinamide is effective in protecting axons from degeneration in EAE, with direct effects on microglia. Overall, this shows the potential of safinamide as an effective neuroprotective agent in MS.


Authors: Morsali D, Bechtold D, Lee W,

Source: Brain. 2013 Mar 20. [Epub ahead of print]

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