Approximately 1 in 17 UK people have a rare disease and the majority have no treatment. Many are neurological diseases and rarity makes clinical trials to develop treatments very difficult. Head-to-head trials comparing drugs are even more difficult to deliver.
The trial, which was conducted at the UCL Queen Square multidisciplinary Centre for Neuromuscular Diseases at the National Hospital for Neurology and Neurosurgery, UCLH, and UCL Queen Square Institute of Neurology, involved 60 adults with confirmed non-dystopic myotonia.
Non-dystrophic myotonia is an example of rare genetic neuromuscular disease that can result in severe life changing disability. Muscle symptoms begin early in life causing mobility problems significantly reducing quality of life and employability.
There is no cure, but in 2012 the same UCL team led and published in JAMA* a multi-centre international trial that repurposed mexiletine, a sodium channel blocker, and showed it was effective and improved quality of life. This trial resulted in mexiletine becoming the first-line treatment for non-dystrophic myotonias world-wide. However not all patients responded, one-third develop significant side-effects and mexiletine cannot be prescribed during pregnancy, when myotonia often worsens. Furthermore, pharma licensing has made mexiletine very expensive and access is restricted.
The UCL team hypothesised that Lamotrigine, a different sodium channel blocker used in epilepsy, could be an alternative. They designed and delivered a head-to-head trial and provided convincing evidence that lamotrigine is as effective as mexiletine, but importantly, was better tolerated and can be used in pregnancy.
Dr Vinojini Vivekanandam, chief investigator (Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology) said
“The trial results are very exciting and important for patients with this muscle channelopathy- based on this trial data, we have already developed a personalised treatment algorithm that is changing clinical practice”
Professor Michael Hanna, senior author (Director of UCL Queen Square Institute of Neurology) said “ Drug repurposing is an important strategy in developing treatments for rare diseases. This is the first head-to-head trial in a rare muscle disease and the results will directly inform patient care and provide more “real-world” options for patients.
Links
- Vivekanandam, V. et al. Mexiletine versus lamotrigine in non-dystrophic myotonias: a randomised, double-blind, head-to-head, crossover, non-inferiority, phase 3 trial. Lancet Neurol 2024; 23: 1004–12
- Professor Michael Hanna's academic profile
- Dr Vinojini Vivekanandam's academic profile
- Queen Square Centre for Neuromuscular Diseases
- UCL news item
* Statland JM, Bundy BN, Wang Y, et al. Mexiletine for Symptoms and Signs of Myotonia in Nondystrophic Myotonia: A Randomized Controlled Trial. JAMA. 2012;308(13):1357–1365. doi:10.1001/jama.2012.12607