Inhibiting the release of glucose into the bloodstream using a plant-based compound
By Alexandria Daum
Project Investigators: Dr. Stephen Withers, Dr. Joerg Bohlmann and Dr. Gary Brayer
Thanks to a common garden flower, a GlycoNet project is making progress on a new therapy to help diabetics keep their blood glucose levels stable.
Dr. Stephen Withers has discovered a compound called Montbretin A, which comes from the common garden plant called Montbretia. He plans to use this compound to control the release of glucose into the bloodstream.
When we eat meals containing starch, it is degraded to glucose in our digestive system by enzymes, before being released into the bloodstream. For people with diabetes, whose bodies are unable to balance their blood glucose levels, a flood of glucose – high blood sugar – can cause serious complications, including kidney and nerve damage.
“If you could inhibit those enzymes – develop molecules that would slow those enzymes down – then you could slow the release of glucose into the bloodstream,” explains Withers, a professor at the University of British Columbia and lead investigator on this project.
While there are two drugs on the market that achieve a similar end, they come with a variety of unpleasant side effects, meaning that many people do not take them as they should. Withers and his team have tested Montbretin A on diabetic rats and found that it slows the release of glucose and has limited side effects, making it an ideal therapy.
Withers is optimistic about the potential of the drug, especially given the growing diabetes epidemic around the world. The Canadian Diabetes Association estimated that in 2015, 3.4 million Canadians were living with diabetes, and an additional 5.7 million – 22 per cent of the population – have pre-diabetes. Pre-diabetes occurs when blood glucose levels are elevated, and about 50 per cent of pre-diabetics will develop Type 2 diabetes in their lifetime.
“It’s a situation that’s going to need multiple different approaches,” says Withers. “What we’re developing is not a cure, but we’re going to need other control means – and one such means is the sort of molecule we’re talking about.”
Now the team, consisting of Withers, Dr. Joerg Bohlmann and Dr. Gary Brayer, are looking at scaling up the production of Montbretin A. Bohlmann is specifically working on understanding how Montbretia synthesizes the Montbretin A compound, with the goal of providing an alternative supply.
“The key thing we need to know now is if we could ever produce sufficient quantities to deal with the market size that is potentially there,” says Withers, who estimates that the drug may be needed to treat tens of millions of people.
The team plans to use a GlycoNet commercialization grant to produce enough Montbretin A to carry out a large animal study. If they get promising results, they hope to move on to a human clinical trial in partnership with a start-up pharmaceutical company called Montbretin Therapeutics and Health Canada.