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

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.

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.