Getting Back at Celiac: Enzyme treatment might stem wheat intolerance

A combination of two enzymes could eventually treat celiac disease, an inherited digestive disorder that affects about 1 percent of people worldwide.

People with this condition, also known as celiac sprue, can’t tolerate gluten, a protein present in grains such as wheat, barley, and rye. When celiac patients ingest the protein, it sets off an immune response that inflames the small intestine and leads to weight loss, diarrhea, and other symptoms.

Currently, the only effective therapy for celiac disease is for patients to exclude gluten-containing foods from their diets. However, since the protein lurks in many nongrain foods, people can have a hard time completely eliminating dietary gluten. “If you wanted to buy a soup or any yogurt or some kind of product that didn’t overtly have bread or pasta … chances are it still contains gluten,” says Chaitan Khosla of Stanford University.

Seeking an alternative approach, Khosla and his colleagues looked to an enzyme derived from barley. When a barley seed is ready to sprout, this enzyme, called EP-B2, breaks down a gluten component called glutamine and thereby frees up starches that nourish the growing plant.

To see whether the enzyme might break up gluten in patients’ stomachs, Khosla’s team first equipped lab-grown Escherichia coli bacteria with the gene for EP-B2. The maneuver turned the microbes into enzyme-making machines.

The researchers then added the product to simulated stomachs: test tubes containing various stomach acids along with doses of gluten. Other test tubes received identical measures of stomach acids and gluten, but no EP-B2.

After an hour, the researchers took samples from all the test tubes and added them individually to lab dishes containing immune cells from people with celiac disease. The samples in which the gluten had remained intact prompted the cells to quickly multiply, indicating a raging immune response. Immune cells exposed to the enzyme-treated gluten reproduced at a slower rate.

However, Khosla notes that even the immune response brought on by the enzyme-treated gluten was beyond what scientists currently consider safe. To further digest gluten, the researchers devised a similar experiment with prolyl endopeptidase (PEP), a well-studied digestive enzyme that breaks up another gluten component called proline.

Like EP-B2, PEP alone didn’t adequately dampen the immune response. However, when the researchers exposed cells to gluten treated with both enzymes, the cells’ division slowed to a crawl.

Khosla’s team presents these results in two reports in the June Chemistry & Biology.

Khosla explains that someday patients with celiac disease might take these two enzymes in a pill with gluten-heavy meals, much as lactose-intolerant people can take a pill if they want to eat dairy products.

“It’s a very attractive idea,” says Peter H. R. Green, a celiac disease researcher at Columbia University. However, he notes that even if such a pill comes to market, it’s unlikely that it will replace careful eating and a doctor’s care.

“The worrying thing to me is the idea of people taking a pill and not having the correct therapy,” Green says.