It hides in foods you know about — bread and pasta — and in those you might not expect: salad dressing, soy sauce, ground spice mixes and pie filling, for example. And all it takes is 100 milligrams — a few crumbs or drops — to trigger illness in a person with celiac disease. What is this sneaky little protein? Gluten. The good news is that its days of wreaking havoc on the digestive system may soon be over.
Ingrid Swanson Pultz, Ph.D. ’12 (microbiology), co-founder and chief scientific officer of PvP Biologics, has designed an oral therapeutic that renders gluten harmless, a breakthrough that could radically change the lives of those suffering from celiac disease.
Ambushed by Gluten
Affecting 2.4 million people in the United States, celiac disease is a disorder where the immune system attacks and damages the small intestine when gluten is ingested. Gluten, which originates in wheat, barley and rye, has infiltrated many a meticulously prepared meal — sometimes hitching a ride on contaminated food surfaces or lurking in processed foods.
When celiac sufferers are ambushed by gluten, they can experience severe abdominal pain, vomiting, diarrhea and headaches, among other unpleasant symptoms. “They can also develop long-term health issues like malnutrition, osteoporosis and rare cancers like lymphoma,” says Shirley Paski, M.D., a gastroenterologist at Cedars-Sinai Medical Center.
The only treatment for celiac disease is to eliminate gluten from the diet, a lifestyle that is both expensive and difficult to maintain. However, Pultz has developed a remedy that could lift the burden of this disease: KumaMax. It’s an enzyme in the form of a pill that breaks down gluten in the stomach, before it gets to the intestines where an immune response can be triggered.
KumaMax could fundamentally change the way people with celiac disease live their lives: at home, at work and with their friends. And it goes beyond eating. “Food is such an integral part of social interaction,” says Paski. “If clinical studies show efficacy, KumaMax could allow people to broaden their diet a bit and not worry so much about trace contamination of gluten.”
It Takes a Team
In 2011, Pultz, then a graduate student in UW Medicine’s Department of Microbiology, was advising a group of undergraduates participating in the
International Genetically Engineered Competition (iGEM). Student teams collaborate to solve real-world challenges by designing new molecules or biological systems. “Some of the students had friends with celiac and wanted to create a therapy for the disease,” says Pultz.
The team had their work cut out for them. Many scientists, with many more years of experience, had already tried to identify a naturally occurring enzyme that breaks down gluten, but they always ran into the same snag — the enzymes they found couldn’t survive the acidic environment of the stomach. “So we tried a different approach — first find an enzyme that could withstand the harshness of the stomach and then engineer it to break down gluten,” says Pultz.
Pultz and her team had experience collaborating with the Institute for Protein Design (IPD) at UW Medicine, known for its expertise in designing and researching new proteins to improve human health. With the help of cutting-edge software, Pultz and her team identified an enzyme and then customized it to attack gluten.
With the creation of the KumaMax prototype, the UW’s team became the first U.S. team to win the iGEM competition. Then Pultz arrived at a crossroads. She and the students were graduating. What would become of KumaMax?
“This enzyme was too promising to just let it languish on a shelf, so I took it on as a translational investigator at the IPD,” says Pultz.