MONTREAL, July 19, 2023 – Myotonic dystrophy type 1, or DM1, is a rare incurable disease that affects the muscles of people with this condition. The researchers and physiotherapists Nicolas Dumont of CHU Sainte-Justine and Elise Duchesne of Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay–Lac-Saint-Jean have identified a new mechanism of action involved in this disease. Combining their clinical and fundamental expertise, they identified a molecular "signature" linked to the muscular deficiencies of this disease by studying muscle stem cells. This major breakthrough has resulted in identifying a new biomarker linked to disease severity and to the development of a promising therapy to improve muscle functional capacity.

Left : Nicolas Dumont, Photo © CHU Sainte-Justine (Véronique Lavoie)
Right : Elise Duchesne, Photo © CHU CR-CSIS (Justine Latour)

The results of this study were published today in the journal Nature Communications.

The study findings bring hope to all those affected by DM1, and in particular to Adam, who has been involved in various research projects at CIUSSS du Saguenay–Lac-Saint-Jean.

"I didn't know I had the disease until quite late in life, at the age of 35, even though by my twenties I was already experiencing muscle spasms and other discomforts. In my first job as a teacher, I found it difficult to smile because my facial muscles kept drooping, which intimidated the children of the elementary school. I now work in a company, at a job that allows me to sit still and be productive even with my limitations. Despite my illness, I have a beautiful, fulfilling life! In my extended family, there are about twenty people suffering from DM1 and three more in my work environment. And the disease doesn't just affect the muscles. It can take many forms and affect sleep, digestion, eyesight, heart rate, the reproductive system, dexterity and so on. It can be very inconvenient. I want my son and everyone affected to benefit from the advances in research. "

© Courtesy of Adam Smith

The need for collaboration in rare disease research
DM1 is a disease that affects one in 8,000 people worldwide, but in Saguenay–Lac-Saint-Jean, it is markedly prevalent, with one in 500 people affected. The region is a living laboratory for the study of several rare diseases, including DM1. A number of researchers have generated a wealth of clinical knowledge over the past four decades through cohort studies. Elise Duchesne, who is also a full professor at the Université du Québec à Chicoutimi, is one of these researchers. Over the past 10 years she has built up a significant tissue biobank that includes numerous muscle biopsies collected from people with DM1. For this study, she joined forces with Nicolas Dumont, expert in the field of muscle stem cells, to help advance knowledge of this disease. Collaboration among researchers of rare diseases is vitally important due to their rare and complex nature.

Molecular signature in DM1 linked to muscle deficiencies
Muscle stem cells play an essential role in the growth and regeneration of muscle fibres. In DM1, the regeneration process is impaired. Nicolas Dumont, who is also associate professor at the Université de Montréal, conducted in-depth analyses that generated a complete list of deregulated genes in muscle stem cells from people with DM1. This molecular signature identified a subgroup of aging muscle stem cells, also known as senescent cells, that produce an inflammatory environment toxic to healthy cells.

Pursuing their work, the research team demonstrated that the level of expression of interleukin 6, one of the molecules expressed by dysfunctional cells, is strongly linked to the muscle weakness and functional disabilities experienced by those with the disease. A simple blood test can indicate the severity of muscle functional limitations and could thus guide clinicians in their work.

A promising therapeutic approach
With this new knowledge, Nicolas Dumont and his team tested a number of senolytics, drugs that can specifically eliminate senescent cells, to identify a new therapeutic approach. Researchers demonstrated that one of the senolytics is effective in eliminating senescent muscle stem cells, thus reducing the toxic inflammatory environment, without affecting healthy cells. This drug is already being used in clinical trials for other conditions. In laboratory tests with this molecule, muscle stem cells from people with DM1 regained the ability to multiply, thus promoting the regeneration process. The same result was observed in experiments on mice. "These findings hold enormous promise," says Nicolas Dumont. "Our objective is to continue our analyses, in order to potentially conduct clinical trials that can demonstrate the efficacy of this treatment in people with DM1."

"For DM1 patients, this is a major step forward. Not only are we now able to better understand this rare disease, but we have information that will help improve the continuum of care and services. This breakthrough shows the importance of collaboration among research teams. This knowledge was generated through the combined efforts of researchers at CIUSSS du Saguenay–Lac-Saint-Jean and CHU Sainte-Justine, who combined their respective expertise, and thanks also to our regional pool of DM1 patients and the large tissue bank we have at our disposal," states Elise Duchesne.