Aug. 3, 2016

Enzymes from carnivorous plant could help people digest gluten

Cumming School researcher David Schriemer looks to pitcher plant for clues to treating celiac disease
University of Calgary researcher David Schriemer has been investigating the enzymes of a species of tropical pitcher plant which show promise in assisting the human digestion of gluten linked to celiac disease.

David Schriemer has been investigating the enzymes of a species of tropical pitcher plant.

Riley Brandt, University of Calgary

Enzymes from a carnivorous plant found in tropical rainforests could potentially help David Schriemer’s niece.

“She was diagnosed about three or four years ago with celiac disease,” says Schriemer, an associate professor at the University of Calgary’s Cumming School of Medicine. “We often joke about my niece being a guinea pig in the lab, but she hasn’t offered yet.”

In a possible step toward eventually developing an effective pill that could potentially help people with such illnesses, Schriemer’s lab led the research behind a study that was released Aug. 2 in Scientific Reports, a journal published by Nature. It details two enzymes used in digestion by pitcher plants, which show particular promise in assisting the human digestion of gluten linked to celiac disease.

“I think it opens up a completely new paradigm for treating celiac disease that we really need to explore further, and at a clinical level,” says Schriemer. A further study summarizing the discovery of the active enzymes in the plants was published July 22 in the Journal of Proteome Research.

Affecting about one out of every 100 people in North America, celiac disease is caused by an abnormal immune response to gluten, a mixture of proteins found in grains such as wheat, rye and barley. In people with the genetic predisposition, it can lead to the production of antibodies that may attack internal organs such as the small intestine.

Patients must follow gluten-free diet 

The resulting damage may not only limit the body’s ability to absorb nutrients, but eventually lead to illnesses such as bowel cancer. While signs of celiac disease may range from abdominal pain and bloating to chronic diarrhea, fatigue and weight loss, many people do not display any overt symptoms. There is currently no cure, meaning patients must follow a strict gluten-free diet.

This can be a major inconvenience, not only because many prepared foods contain gluten. In order to accommodate celiac patients, families must prepare more expensive non-gluten meals using different kitchen implements and containers, making sure there is no cross-contamination with regular meals.

Besides his niece, Schriemer has a “sister-in-law who is so sensitive that if she is contaminated with gluten, she is actually lethargic for a week,” he says. “This could be as minor as using a knife that someone else has used to cut a piece of bread, and there didn’t seem to be any obvious crumbs on it or anything like that.”

As a researcher in the Department of Biochemistry and Molecular Biology at the Cumming School, Schriemer has been investigating the enzymes of a particular species of tropical pitcher plant found in places such as the rainforests of Indonesia and New Guinea. Part of a genus of carnivorous plants that contain traps filled with a special fluid — allowing them to consume prey such as insects to gain nutrients lacking in local soils — Nepenthes ampullaria also digests fallen leaves.

David Schriemer is studying whether the enzyme blend in a species of tropical pitcher plant could be developed into a pharmaceutical product to help people with gluten intolerance.

Schriemer is studying whether the enzymes could be developed into a product for gluten intolerance.

Enzymes discovered in pitcher plants

Although Schriemer initially studied the plants as a source of new reagents or compounds that could be used as tools in protein analysis, “along the way, we discovered a set of enzymes from the fluid that work extremely well in digesting gluten in a way that is directly translatable to human patients,” he says. He zeroed in on nepenthesin and neprosin, the latter a previously unknown enzyme that can break up toxic food peptides into smaller, non-toxic ones.

“We’ve established that you can actually digest a significant amount of gluten under conditions that will work in a human stomach, and we have research spanning all the way from basic discovery through proof in animal models that this can reduce inflammation,” says Schriemer, who is also facility director of the Southern Alberta Mass Spectrometry (SAMS) Centre at the Cumming School.

The discovery is an offshoot of years of basic research involving proteomics, the study of the proteins (proteome) that carry out much of the work within cells. Schriemer probes the proteome using mass spectrometry, a technique of chemical analysis based on the sorting of ions according to their mass.

The enzyme blend has turned out to be about a thousand times more potent in digesting gluten than “any similar concept that is out there,” he says. “For the existing potential options to have any effect, you would pretty much have to consume as much enzyme as you are consuming gluten.” No effective treatment of this kind has yet been approved, says Schriemer.

Gluten important source of protein 

Celiac patients find it difficult to follow a gluten-free diet, he says. “They have a real hard time, whether through personal choices or unintended gluten contamination in a host of modern foods and products, so the idea is to develop the discovery into an enzyme supplement (taken as a pill) that will help them digest gluten before it causes any problems in the small intestine.”

Much like rice, wheat is an important staple, he says. “It’s a key part of our diet. Gluten protein is by far the most abundant protein in wheat, so we shouldn’t discount it because at some level, protein is protein, regardless of whether that is plant-based or animal-based. They provide essential amino acids for our body to function.”

Besides celiac disease, the enzyme blend could also help with separate illnesses such as dermatitis herpetiformis and pancreatic enzyme deficiency, says Schriemer, who is also a member of the Cumming School’s Arnie Charbonneau Cancer Institute. With the help of an American investor, he has formed a company called Nepetx LLC in Florida to “begin developing a possible pharmaceutical agent.”

While it’s likely to be a “multi-year road” before the enzyme blend can be marketed, approval won’t take as long as “is normally the case because the risk is reduced,” he says. “What’s pretty cool about this is that the pitcher plants, and their secretions, have a history of being consumed. The enzymes are very well tolerated in model organisms, so it’s a matter of producing the enzymes and then proceeding through to clinical trials.”