Ion Channel Modulation as a Therapeutic Approach in Multiple Sclerosis.

Abstract:

: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.

journal_name

Curr Med Chem

authors

Arnold R,Huynh W,Kiernan MC,Krishnan AV

doi

10.2174/0929867322666151029104452

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

4366-78

issue

38

eissn

0929-8673

issn

1875-533X

pii

CMC-EPUB-71410

journal_volume

22

pub_type

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