An international multi-centred trial published in the leading medical journal JAMA (The Journal of the American Medical Association) this week, demonstrates a significant treatment benefit using the repurposed cardiac drug, mexiletine, in a genetically stratified cohort of patients with the rare genetic neurological disorder, non-dystrophic myotonia. Professor Michael Hanna, Director of the MRC Centre for Neuromuscular Diseases led the UCL team including MRC clinical training fellow Dr Dipa Raja Rayan as the top recruiting site in this international trial. 

Patients with non-dystrophic myotonia have genetic mutations that result in increased opening of the skeletal muscle voltage-gated sodium channel (NaV1.4) leading to membrane hyperexcitability and manifesting as significant clinical myotonia (stiffness from impaired muscle relaxation). The disorder is estimated to affect approximately 1 in 100,000 people causing debilitating stiffness, pain, weakness and fatigue. It can have a significant impact on patients’ ability to work and quality of life, therefore finding an effective treatment is important.  Mexiletine, is a class 1b anti-arrhythmic drug that acts by blocking sodium channels in the heart and skeletal muscle but has been superseded by more modern drugs for the treatment of arrhythmias. 

The double-blind randomised placebo-controlled experimental medicine Phase II study was carried out in 59 genetically stratified  patients at seven neuromuscular centres in four countries, the largest number of which were recruited by Professor Hanna’s group in the UK. The study clearly demonstrated that mexiletine significantly reduced patient-reported symptoms of stiffness, pain, weakness and fatigue as well as electrically measured myotonia and quantitative grip myotonia in patients compared to placebo.

The study demonstrates that it is possible to perform robust phase II experimental medicine clinical trials with impact in rare diseases through leading international collaboration and effective rare disease networks.

Full study: JAMA mexiletine study

Editorial: JAMA Editorial

JAMA homepage: http://jama.jamanetwork.com/journal.aspx