Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Celiac success: New enzyme efficiently degrades gluten in 'human stomach' environment

03.07.2006
End of the gluten-free diet in sight?

A new enzyme originally developed for commercial food processing turns out to also quickly and nearly-completely break down whole gluten molecules as well as the T cell stimulatory peptides that cause celiac disease, a digestive disease with no current effective treatment other than avoiding wheat, barley or rye products.

In addition, the enzyme operates best in just the kind of physiological environment found in the human stomach and works 60 times faster than an earlier promising enzyme, which was not effective in acidic conditions and was inactivated by pepsin, both of which are found in the stomach.

"On the basis of our results, there now is a realistic chance that oral supplementation with an enzyme can ensure gluten degradation in the stomach before reaching the small intestine, where it causes problems for people with celiac disease," according to Frits Koning, researcher at the Leiden University Medical Center, The Netherlands, who headed the team that has published a new research paper on its work.

The paper, "Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease," is in the online American Journal of Physiology- Gastrointestinal and Liver Physiology, published by The American Physiological Society. Research was by Dariusz Stepniak, Liesbeth Spaenij-Dekking, Cristina Mitea, Martine Moester, Arnoud de Ru, Renee Baak-Pablo, Peter van Veelen and Frits Koning of Leiden University Medical Center, the Netherlands, and Luppo Edens of DSM Food Specialties, Delft.

Clinical trials are likely next step

The new prolyl endoprotease (PEP) that was studied is derived from Aspergillus niger (AN), a common fungus. Strains of A. niger are used in industrial production of citric and gluconic acid as well as producing several food grade enzymes.

Because there are no animal models of celiac disease, "the in vivo efficacy of AN-PEP for gluten detoxification will ultimately have to be addressed in clinical studies involving celiac patients. AN-PEP appears to be a prime candidate for such clinical trials," the paper concluded. As for the timing of any such trials, Koning said: "This is an option the team hopes to explore in the future."

A disease of many paradoxes

Celiac disease affects about 2 million Americans and is also found in Europe, India and parts of the Middle East. It's caused by an uncontrolled immune response to wheat gluten and similar proteins of rye and barley that cause diarrhea, malnutrition and failure to thrive because it inhibits nutritional uptake.

"It's a Caucasian disease with a wide spectrum of symptoms; not all patients are equally affected, but we do not understand why this is the case," Koning said. "It is known to be associated with the HLA-DQ2 gene," he noted, "but while about 25% of the white population has this gene, only about one in 100 get the disease, so it's really a quite puzzling disease in many ways."

Currently the only way to elude the disease symptoms is by avoiding wheat, barley and rye products. "It sounds easy, but gluten especially is widespread in Western diets," Koning said. Gluten is often used as a food additive because it adds protein content inexpensively and also gives dough its elasticity and stickiness, which helps in manufacturing. For instance, Koning said: "Celiac patients can eat potato chips, but not if they have added paprika or other spices because they're 'glued' to the chip with gluten."

AN-PEP outstrips earlier enzyme by 60-fold

Earlier attempts at finding non-human proteases for gluten detoxification (first proposed in the late 1950s) focused on prolyl oligopeptidases (POP), most notably FM-POP, which was able to break down gluten sequences in vitro. However FM-POP's optimal operating pH is between 7 and 8, so it didn't work well in the more acidic stomach pH that goes down to 2 at one stage. A combination of pH 2 and pepsin "immediately inactivated FM-POP," the paper said. AN-PEP, on the other hand, is active from pH 2-8, with optimum effect around pH 4. The combination of pH 2 and pepsin didn't affect AN-PEP activity.

"An effective enzymatic treatment for celiac diseases requires means of destroying all or at least the vast majority of gluten derived T cell stimulatory sequences," the paper said. The key to this is to break the large gluten molecules (large peptides and intact proteins) into smaller pieces before they leave the stomach. Because food stays in the stomach one to four hours, speed of protein degradation is also important. Mass spectrometry comparisons showed that "degradation of gluten peptides by AN-PEP was on average [about 4 minutes, or] 60 times faster than degradation by FM-POP," the paper reported.

In addition to its ability to perform as a potential oral enzymatic therapy because it "is capable of degrading intact gluten molecules and T cell stimulatory epitopes from gluten into harmless fragments" AN-PEP has several additional commercial advantages, the paper said: "The enzyme is extremely stable and can be produced at acceptable cost at food grade quality in an industry setting."

Celiac disease is an HLA-linked disease related to Type 1 diabetes and rheumatoid arthritis in which autoimmune reactions cause the disease; similarly, immune reactions can lead to organ transplant rejection. Koning said it "isn't likely that AN-PEP would be of any therapeutic value in any of these HLA-associated diseases" because Type 1 diabetes and rheumatoid arthritis are real autoimmune diseases, where the immune system attacks parts of the body. In celiac disease, it is the gluten that is the target, not the body.

Reminder warning on early introduction of gluten products

Koning said feeding wheat (or barley or rye) products to infants before they're 6 months old isn't recommended because once an immune response develops "immuno-memory builds up and it doesn't go away." Indeed, Koning noted that in Sweden some years ago gluten was introduced into baby food, which led to a five-fold increase in celiac disease. The problem disappeared when gluten was removed.

Mayer Resnick | EurekAlert!
Further information:
http://www.the-aps.org

More articles from Life Sciences:

nachricht Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg

nachricht Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Electrode materials from the microwave oven

19.10.2017 | Materials Sciences

New material for digital memories of the future

19.10.2017 | Materials Sciences

Physics boosts artificial intelligence methods

19.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>