Advertisement
 

New hope for celiac disease sufferers?

Researchers look at oral enzymes and immunotherapy as possible treatments for celiac disease.

December 21, 2009|By Cathryn Delude
  •  
  (Chip Somodevilla, Getty…)

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.

Still, it is very difficult to eliminate gluten entirely. It lurks in disparate sources such as vinegars, soy sauce, medications, lip balm and Play-Doh (which some children consider edible); and even gluten-free foods, which are expensive, may contain enough traces to cause symptoms. "When we study celiac patients who have been doing their best to follow a gluten-free diet, even after five years we see lots of damage in the small intestines in about half of them," said Dr. Robert Anderson, a gastroenterologist in Melbourne, Australia, who is working on a vaccine to prevent or switch off the reaction to gluten.

His is one of many efforts underway to develop new, non-dietary treatments for celiac disease. Ultimately, celiac patients may be able to take a pill before a meal so they could, 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 therapy

Within 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 either a drug or 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.

The larazotide approach leaves the gluten peptides, or small fragments of proteins,intact but aims to prevent them from penetrating beneath the lining of the gut into the mucous layer where the immune reaction occurs. In celiac disease, as in many autoimmune diseases, including Type 1 diabetes, this intestinal barrier is "leaky" or permeable.

Larazotide is a bioengineered drug designed to close those leaks to keep out gluten and prevent or reverse the disease. In preliminary results from about 300 patients in Phase I and II trials, the drug did seem to benefit patients, who had fewer adverse symptoms after eating gluten. It also reduced the levels of the antibody that serves as a blood marker for the immune response to gluten. But interestingly, the drug did not seem to reduce intestinal permeability.

"So the drug works, but maybe through a different mechanism that we don't understand yet," said Green, who is on the clinical advisory board for both Alba and Alvine. He predicts that, if ultimately found effective, the oral enzymes and larazotide would be marketed as supplements to a gluten-free diet but that many patients would want them to actually replace the restrictive diet. It's unclear not only whether such a use would be possible but also whether it would be a daily regimen or followed only when dining out or traveling, for instance.

Immunotherapy

Advertisement
Los Angeles Times Articles
|
|
|