Health Canada has approved a new antidiabetic treatment derived from a garden flower for phase 1 human trials. GlycoNet researcher Stephen Withers anticipates that the compound could be used to develop a treatment with fewer side effects than other options currently available to people with type 2 diabetes.
Antidiabetic treatment: The natural compound called Montbretin A (MbA) works by inhibiting the alpha-amyla enzyme
“Our approach is to slow down the degradation of the starch component of food. But it doesn’t affect simple sugars, ”says Withers, principal investigator and professor at the University of British Columbia (UBC).
The natural compound called Montbretin A (MbA) works by inhibiting the enzyme alpha-amylase. When MbA inhibits the enzyme alpha-amylase, the starch does not break down immediately and instead travels to the lower part of the intestine.
THAT’S HOW IT WORKS:
Normally, the enzyme alpha-amylase breaks down starch in foods like rice and bread into complex sugars called oligosaccharides. The oligosaccharides are then further degraded by alpha-glucosidase enzymes in the intestinal wall. Releasing glucose into the bloodstream, causing blood sugar levels to spike in type 2 diabetics.
Current drugs that target the same enzyme system often inhibit the alpha-glucosidase enzyme. Preventing the degradation of oligosaccharides or complex sugars and preventing the release of glucose.
“The downside to these drugs is that the derived oligosaccharides provide ‘fast food’ for the gut bacteria further down. And these gut bacteria produce a lot of gas as a by-product. So the patient tends to suffer from diarrhea and flatulence ”, explains Withers. “As a consequence, they don’t tend to take the drug.”
It is hoped that it could be a drug to control blood glucose levels
Withers hopes that MbA could be a drug to control blood glucose levels with fewer side effects than existing drugs in this class. So type 2 diabetics will be more likely to take it. Since MbA prevents starch from breaking down into oligosaccharides, the entire starch polymer will reach the lower intestine. “The bacteria down there can degrade that, but we anticipate that they will do so much more slowly,” says Withers.
From flower to treatment
Withers and UBC researcher Gary Brayer spent many years studying the enzyme alpha-amylase and first tried to develop a compound in the laboratory that could inhibit the enzyme. Before directing your search to nature.
“We were lucky to have in our hands a library with a collection of extracts from different plants from around the world. We had 30,000 such extracts and we were able to screen those extracts for potential enzyme inhibitors, ”says Withers.
Withers selected the most promising extract from the Montbretia flower (Crocosmia x crocosmiiflora). And he worked with UBC researcher Raymond Andersen to isolate and identify the active ingredient: MbA.
“Together with Gary Brayer we discovered how it inhibits amylase, and together with John McNeill we did animal studies in diabetic rats and showed that it controlled blood sugar levels very well,” says Withers.
After the animal studies were completed, Withers worked with JP Heale of UBC’s Office of University-Industry Liaison to request permission from Health Canada to initiate human trials.
The phase 1 clinical trial has been approved but has been delayed due to COVID. The trial will begin as soon as circumstances allow.
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