The decades-old drug mexiletine, which has previously been used to treat abnormal heart rhythms, could treat the symptoms of the genetic muscular disorder nondystrophicmyotonia (NDM), according to BRC-supported research published in the Journal of the American Medical Association (JAMA).
NDMs are not life threatening, but can be debilitating as patients’ muscles contract and won’t relax. Preliminary research, which was carried out in four countries, shows that taking mexiletinecan improve patient-reported stiffness.
The study was carried out in 59 patients at seven neuromuscular referral centres, the largest number of which were recruited through the BRC-supportedMRC Centre for Neuromuscular Diseases.
Professor Michael Hanna, from MRC Centre for Neuromuscular Diseases, led a UCLH/UCL team and was senior author on the paper. He said:
“It is harder to do clinical trials in rare diseases such as nondystrophicmyotonias because individual researchers aren’t able to see the volume of patients required.
“However, if you are a patient with a rarer disease – something which is harder to study – you should still have access to research and treatment.
“That’s why we set up this international collaboration to pool our resources and share information.
“Finding treatments for rarer diseases is an important goal for the NIHR University College London Hospitals Biomedical Research Centre.”
The patients (33 men, 26 women; average age, 43 years) received either oral 200-mg mexiletine or placebo capsules three times daily for four weeks, followed by the opposite intervention for four weeks, with 1-week washout in between.
The main outcome measured for the study was a patient-reported severity score of stiffness, recorded on an interactive voice response (IVR) diary. Secondary outcomes included IVR-reported changes in pain, weakness, and tiredness; clinical myotonia assessment; quantitative measure of handgrip myotonia; and an Individualized Neuromuscular Quality of Life summary score.
There were significant improvements with mexiletine in most other outcomes in the study, including patient-reported outcomes, quality of life scales, and quantitative measures of myotonia (improved myotonia as measured on clinical examination by overall handgrip times in seconds).
Professor Hanna said: “These disorders can be extremely severe and the effects can stop people from working. Patients who took the repurposed drug, mexiletine, reported that their stiffness improved, they had less pain and they also performed better on handgrip tests. The findings are exciting because this treatment can make the difference between patients being able to work and not, but further research is required.”
