Targetting the genetic problem at the heart of myotonic dystrophy
Novembre 29, 2024
By Sophie Lorenzo
Myotonic dystrophy is one of the conditions that are over-represented in Quebec. The Saguenay-Lac-Saint-Jean has the highest concentration in the world, with 1 in 500 people affected compared to 1 in 8000 elsewhere.
This is why the work undertaken at The Neuro is so important. Although breakthroughs for rare neurological disease can benefit patients around the world, Quebecers are the hardest hit and need these the most.
From generation to generation
Myotonic dystrophy is an inherited condition that can affect people of all ages, most often diagnosed in their early 20s. Muscular Dystrophy Canada explains that 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 varies greatly from person to person, but can be seriously disabling. 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,” says Dr. Erin O’Ferrall, a neurologist and principal investigators for neuromuscular trials at The Neuro (Montreal Neurological Institute-Hospital).
Myotonic dystrophy 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.
Because it is a dominant disease, every generation of a family will be affected. And with each generation, the symptoms can be more severe than those of the previous one.
A potential targeted treatment
Available therapies have mainly aimed to alleviate the symptoms of the disease but clinical trials underway at the Neuro Clinical Research Unit (CRU) are testing treatments that have the potential to change the course of the disease.
“It’s very exciting. Until recently, we had nothing that could improve your swallowing, or relieve your breathing difficulties or cardiac arrhythmias. We couldn’t fix these things. This is the first time we could have a treatment that specifically targets the genetic problem at the heart of myotonic dystrophy type 1,” continues Dr. O’Ferrall.
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.
Removing faulty RNA
“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,” explains Dr. O’Ferrall.
If successful, this would be the first time that we have a treatment that would improve the symptoms of the disease, rather than just treating the symptoms without affecting disease progression. While it is still under evaluation, earlier studies were promising.
“Many patients have disconnected from their specialist because there was nothing to offer them. I encourage them to get back in touch with their neurologist because several new treatments are on the horizon,” she concludes.
For more on current trials at the CRU, visit cru.mcgill.ca/nm, or contact 514-398-5500 or info-neuro.cru@mcgill.ca.
