How a carbohydrate-derived dietary supplement could treat muscular dystrophy

GlycoNet researchers identified a natural supplement that could boost muscle fiber formation

By Ali Chou

Every 1 in 3000 individuals in Canada suffer from Duchenne muscular dystrophy (DMD), a rare genetic disease that causes progressive weakness and loss of skeletal and heart muscles. Most patients cannot survive beyond 30 years. With no cure for DMD, treatments like steroid therapy aim to help control the symptoms and slow disease progress, although long-term usage of steroids have shown side effects such as weight gain, high blood pressure, or weak bones.

Now, GlycoNet researchers from Université Laval are investigating a simpler and less complicated treatment that does not involve steroids. Instead, the team led by Dr. Sachiko Sato discovered that a glucose-derived dietary supplement could boost the formation of the muscle fibers to help patients with DMD. The discovery of this glucose-derived molecule as supplement was unexpected, according to Sato. Furthermore, originally, this molecule was not even in their research plan.

“When we sought to the root of the problem, we studied the genes regulating muscle fibers formation,” says Sato. “We found out, to our surprise, that the protein ‘galectin’ was highly expressed in muscle cells and skeletal muscles.” The team was not expecting this result at all, because decades ago, galectins were only classified as a family of carbohydrate-binding proteins without clear implications in the skeletal muscle system. In other words, galectins were not one of the candidates on scientists’ watchlist for DMD research.

Yet, intrigued by the results, Sato used mice in which the gene encoding galectin-3 was removed and saw a reduced muscle force production and an impairment in muscle regeneration by the muscle stem cell when compared to the wild type mice. This confirmed that galectin-3 was critical in maintaining and making muscles, making them a potential therapeutic agent to boost muscle strength in DMD patients.

However, using galectin-3 as a therapeutic agent would be very expensive considering how much muscle mass there is in the human body. “Skeletal muscle accounts for about 40% of our body mass,” says Sato. “This means we would need a lot of synthetic galectin-3 to treat one patient per treatment, and not to mention that DMD patients require life-long treatments to maintain muscle performance.”

Sato thought of a way around it. Instead of using galectin-3—a carbohydrate-binding protein—directly as the therapeutic agent, she proposed to use a small, simple glucose-derived supplement that could indirectly boost the biosynthesis of galectin-3 in the body, which, in turn, through a series of signaling events, incentivizes the body to activate muscle fiber formation.

Using the glucose-derived molecule serves as a more plausible solution than making recombinant galectin-3 to treat DMD. “The supplement is a simple monosaccharide, which is relatively easy to manufacture in large quantity,” says Sato. “In addition, the molecule is soluble in water, so it could be readily prepared in the format of as oral supplement.”

From their preliminary data where mice were treated orally for 2 months with the substance dissolved in water, the team observed an increased size of muscle fiber compared to those who did not receive the treatment. These results are promising, making the team able to move to their next step—testing for longer treatment duration.

Although there are differences between mouse models and human patients, Sato remains confident, saying that this substance has been safely tested on human to treat other illnesses like inflammatory bowel diseases. The team is still carefully gathering toxicity data for their pre-clinical studies and hopes to move the tests into clinical trials to confirm the supplement’s effectiveness on human and to optimize the duration and dosage of the treatment.