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The route to Tolerase® G

Removing dietary and social barriers for the gluten sensitive

It is estimated that up to 10% of people are gluten sensitive to some degree, which can seriously inhibit participation in social situations involving food. DSM addressed this growing health issue by developing AN-PEP, a unique and brand-new dietary enzyme that makes it possible for many gluten-sensitive people to eat and drink outside the home without worry. 

The problem with proline

Intolerance to the protein gluten, which is primarily found in wheat, rye and barley grain, is expressed in different ways, but the main trigger is the same: specific gluten fragments that are exceptionally rich in proline amino acids. Gluten contains an unusually high amount of proline, which already makes the protein somewhat difficult to digest. And the proline-rich gluten fragments are even more challenging. If the body is incapable of digesting them properly, an undesirable physical reaction can occur.

Non-celiac gluten sensitivity

Disease versus sensitivity

The most severe reactions occur in the 1% of the population who suffer from celiac disease, a genetic autoimmune disorder that makes it impossible to safely consume any food that contains gluten. Those with non-celiac gluten sensitivity generally have milder reactions: this is the group the Tolerase G application is designed for. Tolerase G is not intended to replace a gluten-free diet and is not intended to treat or prevent celiac disease.

Extending the solution

DSM Scientist Luppo Edens identified the AN-PEP enzyme: "Gut health has been on DSM’s radar for a long time. We began screening many years ago for an enzyme that would specifically cleave proline-rich protein fragments, making it easier to break down food proteins that cause problems. We had first identified AN-PEP during milk protein allergy research, and realized we could extend the solution to gluten".

Academic expertise

Years of research, development and testing were required to ensure safe and effective application of the enzyme. In this, DSM received indispensable support in an academic partnership with Professor Frits Koning – a renowned gluten and celiac disease expert at the University of Leiden. “The specialized knowledge, technology and techniques at his disposal were essential from beginning to end,” says Edens.

Safe for consumption

The first in vitro tests, which took place in 2006-2008, proved that AN-PEP could break down the problematic gluten fragments, including those in a typical hamburger meal. Subsequent in vivo studies demonstrated the safe character of the enzyme when consumed. This led to its first application in food products that contain gluten.

Oral application capable of degrading gluten in the stomach

Engineering new methods

The scientific efforts then focused on developing an oral application capable of actually degrading gluten in the stomach. The challenge in this was the traditional enzyme-drying process: this did not deliver marketable results in terms of yield, effectiveness and cost. DSM's Engineering Science specialists designed a process that did, and also provided a tablet formulation for customers who might prefer that over powder.

In vivo effectiveness

In 2013, Professor Ad Masclee from the University of Maastricht coordinated in vivo testing in which the action of the AN-PEP enzyme on a gluten-containing meal was directly measured in the stomach of healthy volunteers. By the time the meal reached the small intestine of those who had received the enzyme, almost all gluten had been degraded – unlike in those in the placebo control group.

Protective prophylactic

To date, AN-PEP is the only enzyme proven to be effective in digesting gluten in a human clinical study. Meanwhile, other in vitro studies comparing its effectiveness to five existing gluten digestive supplements confirmed AN-PEP’s superiority. In summer 2015, US manufacturers launched the first dietary supplements containing Tolerase G. The product acts as a prophylactic that enables gluten-sensitive people to consume small amounts of the protein without worries. Meanwhile, a new round of in vivo human clinical trials using gluten-sensitive volunteers finished at the end of 2015. “The final publication is still to take place,” says Human Studies Coordinator Maaike Bruins, “but the data indicates that the conclusions will help further support the evidence. I’m sure this innovative enzyme – whether used to create gluten-free products or as dietary supplement – has a valuable role to play in removing social barriers to those who are gluten sensitive.”

Registration process underway

Removing more barriers

Following its introduction in the US, Tolerase G has now been successfully registered for use in for Australia, New Zealand and the European Union making it available to more gluten-sensitive individuals looking for greater peace of mind while following a gluten-free diet.