An engineered enzyme to disable gluten

By Jason Clevenger

Summary: A group of U.S. based researchers with an eye on developing a pill to treat celiac disease reported the development of a new type of oral enzyme therapy. The group defined the ideal properties of an oral enzyme therapy, which included strong activity in the acidic environment of the gut, a resistance to degradation by other digestive proteases, a high degree of specific binding only to gluten, and ease of production using straightforward protein manipulation methods.

Using these criteria, the group modified a naturally occurring enzyme and optimized it to develop the new therapy, called KumaMax, which could soon find its way into human clinical trials as yet another experimental pharmaceutical treatment for celiac disease.

The researchers concluded the enzyme has “great promise” because of its ability to degrade more than 95 percent of the gluten peptide in acidic conditions.

Conclusion: The use of naturally occurring protein-binding enzymes (known as “proteases”) to disable gluten in the gut before it causes an immune system response is currently being examined in other clinical trials. But this report is the first to describe a computational and chemical engineering approach used to modify and improve a naturally occurring protease. If successful, this type of protein engineering is likely to become an important new direction in pharmaceutical development.


[1] “Computational Design of an α-Gliadin Peptidase”, Gordon SR, Stanley EJ, Wolf S, Toland A, Wu SJ, Hadidi D, Mills JH, Baker D, Pultz IS, Siegel JB, Journal of the American Chemical Society. 2012 Dec 19;134(50):20513-20.