A clinical trial underway at The Neuro’s Clinical Research Unit (CRU) is testing a drug that has the potential to change the course of myotonic dystrophy, not merely treat its symptoms. The disease affects one in 500 people in Quebec’s Saguenay–Lac-Saint-Jean region, the highest concentration in the world. Current therapies mitigate some symptoms but are unable to impact disease progression.
“It’s very exciting,” said Dr. Erin O'Ferrall, a neurologist and principal investigator for neuromuscular trials at The Neuro. “This is the first time we could have a treatment that specifically targets the genetic problem at the heart of myotonic dystrophy type 1.”
From generation to generation
Myotonic dystrophy is an inherited condition that can affect people of all ages, most often diagnosed in their early 20s. It is characterized primarily by a progressive atrophy and weakness of the muscles of the arms, legs, swallowing and breathing, as well as by myotonia: difficulty relaxing a muscle after performing a given movement.
It is a multi-system disease: it can affect the thyroid gland, cause insulin resistance or diabetes, cardiac arrhythmias, cataracts, fertility problems and even intellectual disabilities.
It is also a dominant disease, meaning that a single copy of the mutated gene (from one parent) is enough to cause the disorder. With each generation, the symptoms can be more severe than those of the previous one.
Globally, myotonic dystrophy affects one in 8,000 people.
“It varies greatly from person to person, but can be seriously disabling,” said O’Ferrall. “Patients may have difficulty walking and eventually feeding or bathing themselves. They may have speech impediments, which makes communication difficult. They can have difficulty swallowing, which can lead to choking, lung infections or weight loss.”
Quebec has a particularly high concentration of rare diseases. According to the Quebec Ministry of Health, nearly 700,000 Quebecers are affected or carriers of rare diseases, of which 80 per cent are genetic.
A potential targeted treatment
In myotonic dystrophy type 1 (DM1), there is an accumulation of messenger RNA (mRNA) in the cells that is too large and cannot be eliminated effectively. It accumulates and causes the progressive worsening of symptoms.
“Until recently, we had nothing that could improve your swallowing or relieve your breathing difficulties or cardiac arrhythmias – we couldn't fix these things,” said O’Ferrall.
This new molecule was developed specifically for DM1 and uses small-interfering RNA, along with an antibody to help it penetrate cells, where it interrupts the damaging effects of the faulty mRNA. It also works to remove existing accumulation of defective RNA.
While the new drug is still under evaluation, early phase studies have been promising. The CRU is one of only three sites in Canada among 40 internationally taking part in this randomized Phase III trial, which will confirm the effectiveness and continue to monitor side effects of the treatment. Participants will be assigned to receive either placebo or the investigational treatment. At the end of the study, all participants will be given the option to have early access to the investigational treatment.
This is one of several promising studies underway at the CRU for DM1, with new trials scheduled to open in 2025.
“Many patients have disconnected from their specialist because for years we had nothing to offer them. I encourage them to get back in touch with their neurologist because several potential treatments are on the horizon,” she said.
For more on current trials at the CRU, visit , or contact 514-398-5500 or info-neuro.cru [at] mcgill.ca.
