A commonly used drug could transform the treatment of rare muscle diseases

Lamotrigine, a drug commonly used to treat epilepsy and certain mood disorders, has been shown to be an excellent treatment option for a rare genetic neuromuscular disorder called non-dystrophic myotonia in a world-first study led by researchers at University College London.

The study, published in The Lancet Neurologydetails the “head-to-head” study the researchers conducted to test two drugs, mexiletine and lamotrigine, on people with the disease.

The study, conducted at the UCL Queen Square Multidisciplinary Center for Neuromuscular Diseases and the National Hospital for Neurology and Neurosurgery, UCLH, involved 60 adults with confirmed non-dystrophic myotonia.

Patients were randomly assigned to receive either mexiletine for eight weeks, followed by lamotrigine for eight weeks, or the reverse order, with a seven-day break between treatments. Neither the participants nor the researchers knew at any point which treatment was being administered.

At the end of the study, lamotrigine was found to reduce stiffness – the main symptom of non-dystrophic myotonia – by about the same amount as mexiletine.

The lead researcher Dr. Vino Vivekanandam (UCL Queen Square Institute of Neurology and consultant neurologist) said: “Around one in 17 people in the UK suffer from a rare disease and the majority do not receive treatment. Many are neurological diseases and their rarity is being studied in clinical trials.” It is very difficult to develop treatments.

“Head-to-head studies comparing medications are important to find out which treatments are ideal. The study results are very exciting and important for patients with this muscle channelopathy.”

Non-dystrophic myotonias are life-changing muscle disorders caused by problems with ion channels in the muscles. Symptoms (such as muscle stiffness, pain, weakness and fatigue) usually begin in childhood and can lead to significant disability, affecting quality of life and ability to work. There is currently no cure.

In 2012, the same UCL team led a multicentre international trial that repurposed mexiletine – a sodium channel blocker – and showed it was effective in treating non-dystrophic myotonia and improving quality of life.

As a result, mexiletine became the first-line treatment for non-dystrophic myotonias worldwide.

However, not all patients respond to treatment and a third experienced significant side effects, the most common being reflux or gastrointestinal side effects. In addition, mexiletine cannot be prescribed during pregnancy if myotonia often worsens.

Lamotrigine represents an alternative solution as the study has shown that the drug is well tolerated by patients and offers additional benefits in that it can be used in pregnancy and is less expensive. No serious side effects were reported.

Lead author Professor Michael Hanna (Director of the UCL Queen Square Institute of Neurology and Consultant Neurologist) said: “Drug repurposing is an important strategy in developing treatments for rare diseases. This is the first head-to-head study of this rare muscle disease and the results will feed directly into patient care and provide patients with more “real world” options.”

This research will impact clinical practice worldwide, as mexiletine is often inaccessible in developing countries or expensive in developed countries. The results show that lamotrigine is a comparable treatment and therefore represents an excellent treatment option for affected patients.

Dr. Vivekanandam said: “Based on these study data, we have already developed a personalized treatment algorithm for clinical practice, which is already used in our clinical service, taking into account several aspects of the study and the mechanism of action of lamotrigine mexiletine as well as local economic considerations.