Repurposing of sodium channel antagonists as potential new anti-myotonic drugs

•Sodium channel blockers are the main therapeutic target for myotonia.•Clinical trials to determine best treatment are hampered by disease rarity.•Well designed in vitro pharmacological testing may prioritise agents for clinical use.

Myotonia is often a painful and disabling symptom which can interfere with daily motor function resulting in significant morbidity. Since myotonic disorders are rare it has generally proved difficult to obtain class I level evidence for anti-myotonic drug efficacy by performing randomized placebo controlled trials. Current treatment guidance is therefore largely based on anecdotal reports and physician experience. Despite the genetic channel heterogeneity of the myotonic disorders the sodium channel antagonists have become the main focus of pharmacological interest. Mexiletine is currently regarded as the first choice sodium channel blocker based on a recent placebo controlled randomized trial. However, some patients do not respond to mexiletine or have significant side effects limiting its use. There is a clinical need to develop additional antimyotonic agents. The study of Desaphy et al. is therefore important and provides in vitro evidence that a number of existing drugs with sodium channel blocking capability could potentially be repurposed as anti-myotonic drugs. Translation of these potentially important in vitro findings into clinical practice requires carefully designed randomized controlled trials. Here we discuss Desaphy's findings in the wider context of attempts to develop additional therapies for patients with clinically significant myotonia.