Sustained-release fampridine and the role of ion channel dysfunction in multiple sclerosis

Abstract

Ion channel dysfunction is an important mechanism that contributes to functional disability and axonal degeneration in multiple sclerosis (MS). Recent studies have revealed that there are complex rearrangements of voltage-gated Na⁺ channels that occur with acute brain inflammation in MS, with up-regulation of primitive Na⁺ channel isoforms such as Nav 1.2 during acute inflammation. While these changes may help support neural conduction, increased expression of ‘persistent’ Na⁺ conductances and altered function of the Na⁺/K⁺ pump may contribute to axonal degeneration in MS. Increased expression of K⁺ channels due to demyelination has also been considered as a contributing factor to conduction failure in MS. Recent phase II and phase III clinical trials have demonstrated improvements in walking speed in patients receiving fampridine SR, a K⁺ channel blocker. This medication appears to be well-tolerated with a low risk of serious adverse events and provides benefits in both relapsing and progressive forms of MS.