Ion Channel Modulation as a Therapeutic Approach in Multiple Sclerosis

Title:Ion Channel Modulation as a Therapeutic Approach in Multiple Sclerosis

Volume: 22 Issue: 38

Author(s): R. Arnold, W. Huynh, M.C. Kiernan and A.V. Krishnan

Affiliation:

Keywords: 4-aminopyridine, fampridine, ion channels, K⁺ channels, multiple sclerosis, Na⁺ channels, treatment.

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.

Cite this article as:

Arnold R., Huynh W., Kiernan M.C. and Krishnan A.V., Ion Channel Modulation as a Therapeutic Approach in Multiple Sclerosis, Current Medicinal Chemistry 2015; 22 (38) . https://dx.doi.org/10.2174/0929867322666151029104452