Lamotrigine, a medication typically used for epilepsy and some mood disorders, has recently been identified as a promising treatment for a rare genetic neuromuscular condition called non-dystrophic myotonia, as revealed in a pioneering trial by UCL researchers.
Lamotrigine, a medication typically used for epilepsy and some mood disorders, has recently been identified as a promising treatment for a rare genetic neuromuscular condition called non-dystrophic myotonia, as revealed in a pioneering trial led by researchers from UCL.
The findings, published in Lancet Neurology, described a “head-to-head” trial that compared two medications, mexiletine and lamotrigine, in individuals diagnosed with this condition.
Conducted at the UCL Queen Square Multidisciplinary Centre for Neuromuscular Diseases and the National Hospital for Neurology and Neurosurgery, this trial involved 60 adults diagnosed with non-dystrophic myotonia.
Participants were randomly assigned to receive either mexiletine for eight weeks followed by lamotrigine for eight weeks or the opposite order, with a one-week gap between treatments. Nobody, including the researchers, was aware of which treatment was being administered at any given time.
By the trial’s conclusion, lamotrigine was shown to alleviate stiffness — the primary symptom of non-dystrophic myotonia — to a similar extent as mexiletine.
Dr. Vino Vivekanandam, the chief investigator and a consultant neurologist at UCL Queen Square Institute of Neurology, stated: “Around one in 17 individuals in the UK live with a rare disease, most of which lack effective treatments. Many of these are neurological and their rarity poses challenges for conducting clinical trials. Comparative trials are essential to determine which treatments are most effective.”
“These trial results are incredibly promising and vital for patients suffering from this muscle channelopathy.”
Non-dystrophic myotonias are debilitating muscle disorders due to ion channel deficiencies in the muscles. Symptoms often arise in childhood and can lead to severe disability, adversely affecting one’s quality of life and job prospects. Currently, there is no remedy for this condition.
Back in 2012, the same UCL team led an international multi-center trial repurposing mexiletine — a sodium channel blocker — demonstrating its effectiveness in treating non-dystrophic myotonia and enhancing quality of life.
As a result, mexiletine became the primary treatment option globally for non-dystrophic myotonias.
Nonetheless, not everyone benefits from this medication; a third of patients experienced notable side effects, the most frequent being gastrointestinal issues like reflux. Moreover, mexiletine is not suitable for pregnant women when myotonia often intensifies.
In contrast, lamotrigine offers an alternative option, as the trial indicated that this drug was well-accepted by patients, with additional benefits of being safe for use in pregnancy and being more affordable. No serious side effects were noted.
Professor Michael Hanna, the senior author, Director of the UCL Queen Square Institute of Neurology, and a consultant neurologist, remarked: “Repurposing existing medications is a crucial strategy in formulating treatments for rare diseases. This trial marks the first direct comparison in this uncommon muscle disorder and its outcomes will enhance patient care and expand ‘real-world’ treatment options.”
This study will have a global impact on clinical practices, given that mexiletine is often inaccessible in developing nations or prohibitively expensive in wealthier countries. The findings affirm that lamotrigine is a viable alternative, presenting a valuable treatment option for affected individuals.
Dr. Vivekanandam commented: “Using data from this trial, we’ve developed a personalized treatment protocol for clinical application, which is already being implemented in our service, considering various trial aspects along with the actions of lamotrigine and mexiletine and local economic factors.”
This research received funding from the Neuromuscular Study Group, the Jon Moulton Charity Trust, and a fast track grant from the National Institute for Health and Care Research biomedical research center at UCLH. The team expresses gratitude to the patients and their families for their invaluable support throughout the study.
