Duchenne muscular dystrophy (DMD) is a rare genetic disease affecting approximately one in every 3500 children (almost exclusively males). Although DMD is often inherited, about a third of the time it occurs unexpectedly. DMD causes progressive weakness and muscle loss, with most patients not surviving beyond 30 years.

“The gene responsible for Duchenne muscular dystrophy is dystrophin,” explains GlycoNet researcher and Université Laval professor Sachiko Sato. “Dystrophin is the longest gene in the human genome.”

The size of the gene makes it difficult to target the various mutations that disrupt the production of dystrophin—the protein linked to muscle stability and muscle fibre formation. No cure for DMD is currently available. Some current treatments to slow down progression of the disease include steroid therapy and exon skipping—a technique that “skips over” problematic sections of the gene to correct function.

Sato and her research team are currently conducting preclinical trials of a promising alternative treatment that could reduce muscle damage as much as 50 per cent. This drug is a 100 per cent pure, pharmaceutical-grade version of a monosaccharide (or sugar) called N-acetylglucosamine, which is naturally found in human breast milk.

Previous study results have shown that 10 days of administering the drug via abdominal injection was sufficient to improve muscle function and reduce muscle damage in a mouse model of DMD. Daily injections would not be realistic, however, so the team is looking at oral administration of the drug as well as determining dosage levels.

While steroid therapy remains one of the most common treatments for DMD, long-term use can lead to side effects such as weight gain, weak bones, or high blood pressure. The monosaccharide could provide an alternative treatment, or potentially be used in conjunction with steroids. This co-treatment scenario is being examined as part of the team’s preclinical research.

Sato’s research collaborators at Université Laval include GlycoNet researchers Jérôme Frenette, a skeletal muscle specialist, and Masahiko Sato(h), an expert in imaging software development and analysis.

A serendipitous discovery

“Even though I’m always doing the basic science, I always think about one day, maybe we’ll be able to help patients in some way,” says Sato.

Sato spent many years studying a family of carbohydrate-binding proteins called galectins and their roles in infectious diseases. She was trying out a new microscope and looking at galectin-3 binding one day when she had a thought to examine galectin-3 in relation to muscle fibre generation. After running some tests, she found that galectin-3 plays a role in increasing the speed of muscle regeneration.

However, it would be impossible to deliver galectin-3 to all the muscles in the body, especially as a life-long treatment, given that muscles make up about 40 per cent of our body mass.

Because DMD patients already have galectin-3, Sato searched for an alternative approach to activate this galectin’s muscle regenerating properties.

“We wondered, if we can introduce another type of sugar-protein interaction to help the muscle membrane stabilize and bind to the body, then we might be able to rescue some damage of the muscle caused by the lack of dystrophin,” explains Sato. This led her to examine the monosaccharide that increases the biosynthesis of oligosaccharides, which could bind to galectin-3, thereby boosting muscle fibre formation.

Next steps

If successful as a treatment for DMD, the drug could potentially be used to treat other types of muscular dystrophies, such as Becker muscular dystrophy.

Sato is hopeful that the research team could start clinical trials within the next few years if all goes well with the remaining preclinical research.

“We are very happy that we may be able to hopefully help,” says Sato. “We have quite encouraging data.”

A CHU de Quebec Foundation fundraiser organized by Jacques Nantel is currently raising funds to support the preclinical and clinical research for this DMD treatment.

The research has received funding from Defeat Duchenne Canada (previously Jesse’s Journey), GlycoNet, Canadian Institutes of Health Research, the Canadian Foundation for Innovation, CHU de Quebec Foundation, and Wellesley Therapeutics. The research has also benefitted from collaborations with Willem Wassenaar from Wellesley Therapeutics; Kazuki Nakajima and Yasuhiko Kizuka from the Institute for Glyco-core Research at Gifu University; and Junko Nio-Kobayashi from Hokkaido University.