Novel therapies in development that inhibit motor neuron hyperexcitability in amyotrophic lateral sclerosis

ABSTRACT

Introduction: Motor neuron hyperexcitability appears linked to the process of neurodegeneration in amyotrophic lateral sclerosis (ALS). As such, therapies that inhibit neuronal hyperexcitability may prove effective in arresting the progression of ALS.

Area covered: We searched MEDLINE and ClinicalTrials.gov and selected randomised controlled trials that covered neuroprotective therapy. Riluzole has been established to reduce neuronal hyperexcitability. More recently, initial studies of Na⁺ channel blockers (mexiletine and flecainide) have been trialled. Separately, a trial of a K⁺ channel activator (retigabine) is underway, while edaravone is currently being considered for licensing by drug approval agencies based on a hypothesis that the elimination of free radicals may lead to protection of motor neurones.

Expert commentary: Initial clinical trials with Na⁺ channel blockers have not yet established efficacy in ALS. Currently, retigabine is under evaluation as a potential therapy. Edaravone has recently been approved as a new therapeutic option for ALS in Japan.

KEYWORDS:

• Amyotrophic lateral sclerosis
• hyperexcitability
• riluzole
• mexiletine
• flecainide
• retigabine
• edaravone
• free radical scavenger
• neuroprotective

Declaration of interest

Y Noto is supported by the Nakabayashi Trust for ALS research. K Shibuya, S Vucic and MC Kiernan receive funding to Forefront, a collaborative research group dedicated to the study of motor neuron disease, from the National Health and Medical Research Council of Australia Program Grant (#1037746). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed