Op-ed: Glycomics research supports a cure for Type 2 diabetes from plants

Jörg Bohlmann • Posted: November 30, 2022 • Republished from Healthing

GlycoNet scientists at UBC have found a plant compound that helps control blood sugar levels in people with Type 2 diabetes.

This new anti-diabetic compound derived from the garden flower, montbretia, is approved by Health Canada for Phase 1 human trials. SUPPLIED
Today, diabetes is a global epidemic, with approximately 422 million cases worldwide and constitutes elevated blood glucose levels due to the inefficient use of insulin in the body. More than 5.7 million Canadians are living with diagnosed diabetes (Type 1 or Type 2). In addition, 11.7 million Canadians are living with diabetes or prediabetes, which, if left unmanaged, can develop into Type 2 diabetes (T2D).
 
Roughly half of the western medicines today derive from naturally occurring plant metabolites. Plants produce over 200,000 of these specialized metabolites, but identifying medicinally useful ones is challenging, and obtaining sufficient quantities for human use poses an even more significant challenge.
 
Modern agriculture and plant bioengineering can play an essential role in overcoming the challenge of an insufficient supply of plant metabolites. Therefore biopharming will help utilize the largely undiscovered potential of specialized plant metabolism that may lead to new treatments for improving human health.
 

A promising new way to treat T2D

A few years ago, in an effort to produce a diabetes drug that explicitly inhibits human pancreatic amylase (HPA) activity without having unwanted gastrointestinal side effects, GlycoNet — a pan-Canadian initiative bringing together researchers, industry and academic partners to develop solutions through the study of glycomics — and University of British Columbia (UBC) scientists screened 30,000 extracts derived from plants and other organisms and found a single compound that fit the bill: montbretin A (MbA). MbA comes from the bulb-like underground corms of the ornamental plant montbretia ( Crocosmia  x  crocosmiiflora ). This new anti-diabetic compound derived from a garden flower is approved by Health Canada for Phase 1 human trials. It is also anticipated that the compound could be developed into a treatment for T2D with fewer side effects than other options currently available.

The unpleasant gastrointestinal side of current treatments for T2D often ends in poor treatment compliance. However, there is potential for new drug development that can slow down carbohydrate digestion after a meal, a critical process for controlling blood sugar levels in T2D patients. The unique biological activity of MbA is that it slows down the very first step of the degradation of the starch component of food. MbA is an interesting biomolecule affecting sugar metabolism in the human body. It is also made in part from plant sugar metabolism, creating a confluence of sugar metabolism in plants and sugar metabolism in humans.
 

MbA is currently being developed for the treatment of T2D, but researchers have run into a roadblock to further drug advancement.

But there’s not enough MbA

Montbretia plants produce MbA in minimal amounts for a very short time of the year, and it can’t be produced in large quantities by chemical synthesis. However, scientists from GlycoNet, which is supported by the government of Canada through the federal  le cadre du programme fédéral des réseaux de centres d'excellence (RCE) , and UBC uncovered the complete sequence of genes for a biosynthetic pathway of MbA, utilizing the importance of streamlined collaboration along with funding and support from GlycoNet.

In anticipation that MbA will be successful in human trials, GlycoNet and UBC researchers, in partnership with the Canadian biotechnology industry, are now pursuing a bioengineering strategy to a secure supply of the compound on a large scale. In one approach, MbA-producing genes from the montbretia plant are inserted into yeast cells to create a “biofactory.” In another approach, referred to as biopharming, MbA biosynthesis are being reconstructed into the tobacco plant for future scalable production in vertical farming facilities.
 

Can biopharming and vertical farming be the answer to success?

For the success of MbA as a T2D treatment, we need to enable affordable, reliable and scalable production. Bioengineered tobacco can be grown in a controlled production environment independent of annual growth cycles, which limit MbA supply from montbretia plants. Combined with vertical farming, which has the capability to fit an equivalent of 700 acres (280 hectares) of farmland in a building equivalent to the size of a large supermarket, it is possible to maximize the growth and MbA production potential of bioengineered tobacco.
 
Monitoring sugar highs and lows are part of the realities of diabetic patients. With November being Global Diabetes Awareness Month, we aim to raise awareness and acknowledge the efforts taken to tackle such serious clinical conditions that can be traced or be treated by regulating glucose releases, such as diabetes, nutritional disorders, and certain types of obesity.
 
Bioengineering and agriscience have definitive roles to play in the development of new treatments.
 
Dr. Jörg Bohlmann is a GlycoNet research investigator, Professor and Distinguished University Scholar in the Michael Smith Laboratories at the University of British Columbia, Vancouver.
 
This op-ed was originally published by Healthing.
 




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