Ion channel dysfunction has been identified as a contributor to symptom development
and neurodegeneration in multiple sclerosis (MS). The molecular insights have been
translated into new lines of research, with ion channel modulation now representing a therapeutic
approach in MS. Studies of Na+ channel function have demonstrated pathological
blockade of Na+ channels during an acute inflammatory attack. Relapses are typically associated
with subsequent alterations in Na+ channel expression and structure. However, these compensatory
changes may also be deleterious. Specifically, increased Na+ channel expression may contribute to neuronal
energy insufficiency and a cascade of events that may ultimately lead to neurodegeneration and apoptosis.
Pharmacological blockade of Na+ channels in animal models of MS demonstrated encouraging results, although
mixed results were obtained in subsequent clinical trials in MS patient cohorts. The process involved
in demyelination, a characteristic event in MS pathology, may also induce complex structural changes mediated
by K+ channels that may in turn hinder neural transmission. From a therapeutic perspective, the potent K+
channel blocker, 4-aminopyridine (4-AP), has demonstrated neurophysiological and functional improvements
in animal models of demyelination. Clinical translation of these results was recently achieved with the advent
of Fampridine PR, a modified release form of 4-AP, with phase III clinical trials that demonstrated improvement
in neurological symptoms including fatigue, walking speed and strength in MS patients.