In a sense, the 2 million plus Americans with celiac disease are lucky. No other autoimmune disease has such a safe and effective treatment.
Purging the diet of gluten—the protein in wheat, rye and barley that triggers an immune reaction in the gut—can reverse the disease and reduce intestinal inflammation. That's important, because studies now show that the consequences of untreated celiac disease are graver than previously thought, causing anemia, arthritis, osteoporosis, hepatitis, neurological problems and even malignancies, as well as increased general mortality.
Robert Anderson, a gastroenterologist in Melbourne, Australia, is working on a vaccine to prevent or switch off the reaction to gluten.
His is one of many efforts under way to develop new, non-dietary treatments for celiac disease. Ultimately, celiac patients may be able to take a pill before a meal so they can, for example, have stuffing with their holiday turkey. Or, as is Anderson's goal, they could go for a series of treatments similar to allergy shots that would teach their immune systems to tolerate gluten.
"It's very exciting that the pathophysiology of celiac disease is understood to such a degree that we can design potential therapies," said Dr. Peter Green, director of the Celiac Disease Center at Columbia University College of Physicians and Surgeons in New York.
There are two categories of treatments being developed. One would supplement a gluten-free diet and protect patients from occasional gluten exposure; the other would train the immune system to tolerate gluten and allow patients to eat a regular diet.
Enzyme therapyWithin the first category, one approach uses oral enzymes that target gluten. We cannot completely digest gluten because humans lack digestive enzymes that can break it down, but researchers at Stanford University combined enzymes from bacteria and barley that finish what our own digestive juices cannot. They showed in rats that when gluten is broken down into smaller fragments, it no longer causes inflammation in the intestines. Alvine Pharmaceuticals, based in San Carlos, Calif., has developed this "glutenase" therapy and is now recruiting patients for a Phase II clinical trial.
In this trial, as with the others, participants have had a diagnosis of celiac disease confirmed by a biopsy but have had it under control on a gluten-free diet. They are given a drug or a placebo, along with a gluten challenge, often the equivalent of one or two slices of bread.
"From the early data it looks like the oral enzymes break down enough gluten to be useful," said Dr. Daniel Leffler, director of clinical research for the Celiac Center at Beth Israel Deaconess Medical Center in Boston. Leffler was not involved in the enzyme trial but is an investigator in a nearly completed Phase II trial testing a different drug, larazotide, developed by Alba Therapeutics in Maryland.
ImmunotherapyThe second category of treatment, known as immunotherapy, is more investigational but also more exciting, Leffler said. It would allow patients to eat a regular diet by quelling immune response in the gut. This response is driven by immune cells known as T cells, which react when other immune cells display gluten fragments on their surface.
In Australia, a company founded by Anderson, called Nexpep, is packaging the gluten peptides that trigger this immune response into a vaccine that will desensitize the immune reaction. The theory, which he says works in animals, is that by introducing these peptides through injections under the skin rather than through the gut, the immune cells learn to tolerate them and no longer display them to the T cells. That can theoretically prevent or turn off the reaction that damages the intestines
"If we can figure out how to give the drug, how frequently and when we need maintenance therapy," he added, "then we can use the same principle to explore treatments for other autoimmune diseases." Several other groups are also developing vaccines for celiac disease, but this one is furthest along.