Life Long Gluten Free Diet Treats Celiac Diseases

20/05/08 For those suffering from celiac disease, there may be good news on the horizon. New research presented at Digestive Disease Week 2008 will discuss the latest advancements in the diagnosis and prevention of celiac sprue.

"At this time, the only effective treatment for celiac disease is a lifelong gluten-free diet, a lifestyle that is difficult for many patients to manage," said Peter H. Green, MD, Columbia University Medical School. "Unfortunately, many people are unaware that they have celiac disease, and if left untreated, it can be life threatening. The studies presented will hopefully lead to improved diagnosis, prevention, treatment and quality of life for this disease."

Celiac disease is an autoimmune disorder in the small intestine triggered by the consumption of a common protein called gluten - found in bread, pasta and many other common foods. Though the disease is genetic, it often goes undiagnosed. It is estimated that one in every 100 Americans may be affected by celiac disease.

AT-1001 for the Prevention of Celiac Disease Activation with Gluten Challenge

A new therapy may protect patients with celiac disease from exposure to gluten, according to findings from the first double-blind study ever conducted on celiac disease.

Celiac sprue is a digestive disease that damages the small intestine and disrupts the absorption of nutrients from food. People who have this disease are unable to tolerate gluten, which is found in wheat, rye and barley. Gluten is found mainly in foods but may also be found in common products such as medicines and vitamins. Symptoms of gluten toxicity include diarrhea, weight loss, abdominal pain, anemia and oral ulcerations.

While most people with celiac disease do well on a gluten-free diet, the level of gluten avoidance needed to maintain disease remission represents a significant burden. Further, inadvertent gluten exposure is the leading cause of persistent symptoms in adults with celiac disease. For these reasons, investigators set out to evaluate the safety and efficacy of AT-1001, a medication that may prevent gluten from crossing the intestinal mucosa by reversing barrier dysfunction. The primary outcome was to examine the effect of treatment on intestinal permeability. This involves examining how well the intestine functions by measuring differential absorption of a combination of sugars.

Eighty-six patients with celiac disease were treated with AT-1001 as part of three different groups: gluten-challenged but received placebo AT-1001; no gluten as well as either active or placebo AT-1001; gluten and one of four doses of active AT-1001.

After the first seven days of treatment, patients in all groups improved their intestinal permeability, which was an unexpected outcome, possibly reflecting patients' stricter adherence to a gluten-free diet. At the end of the 21-day study period, participants receiving active AT-1001 were found to have decreased intestinal permeability and less symptoms of gluten toxicity compared to the group receiving gluten and placebo AT-1001.

Still, Daniel Leffler, MD, clinical research director at the Celiac Disease Center at Beth Israel Deaconess Medical Center in Boston, said that while the subjects did improve, the primary study outcome was not met. But he added that the findings are promising enough that investigators are currently conducting a larger trial over a longer time period.

"Even allowing for the fact that people in clinical trials may practice healthier habits, the fact that all of the groups showed improvement in the first week of the study is significant and helps us to plan better celiac studies," said Dr. Leffler. "This work offers great promise for patients who, in the near future, may have a treatment that improves upon dietary restriction alone."

Criteria For Diagnosing Celiac Disease May Be Too Stringent and in Need of Revision

Current diagnostic criteria for celiac disease include small intestinal mucosal membrane villus atrophy and inflammation. But according to new research, these criteria may be too stringent, leaving patients with the disease undiagnosed and untreated.

Researchers studied 145 patients suspected of having celiac disease to determine if the current diagnostic criteria are too narrow. Seventy-one of the patients were found to be endomysial antibody positive, and of those only 48 met the criteria under the current definition of celiac disease. The remaining 23 patients were divided randomly into two groups. One group was placed on a gluten-free diet and the other continued a regular diet that included gluten.

Patients were biopsied again after one year following their respective diets. Investigators found that the patients on the gluten-free diet were asymptomatic, and that their endomysial antibodies disappeared as did their small intestinal mucosal inflammation. However, the patients on a regular diet continued to experience symptoms. These patients continued to be endomysial antibody positive, and showed further deterioration of the small bowel membrane, mucosal inflammation and gluten-induced lesions in the bowel.

According to Markku Maki, MD, professor of pediatrics at the University of Tampere, Celiac Disease Study Group, Tampere, Finland, patients on the gluten-free diet elected to continue the diet after the yearlong study, and the patients on the regular diet elected to eliminate gluten from their diet and over time became symptom free, endomysial antibody-free and experienced healing of the mucosal membrane.

Researchers believe that over time, patients who are endomysial antibody positive may develop the gut injury that makes up the current criteria for diagnosing celiac disease. "By redefining the criteria for celiac disease, we can treat patients before they begin to experience the most severe symptoms and signs of the disease," said Dr. Maki.

Implications of Enzymatic Detoxification of Food Gluten in Celiac Disease

Treatment options for celiac disease have not changed in decades. They remain limited to asking patients to adhere to a life-long gluten-free diet, which is difficult to maintain and can adversely effect quality of life. Humans cannot fully digest gluten; instead, the gluten in food is only partially broken down. In celiacs these remaining gluten fragments are toxic to the intestine, causing intestinal inflammation and damage that can result in the various symptoms of the disease (malabsorption, diarrhea, weight loss and anemia). Many patients however are only mildly affected and may have few if any symptoms

With the hope of broadening treatment options for those with celiac disease, researchers sought to determine if certain natural enzymes given to celiac patients could help fully break down gluten fragments, making the gluten they ingest non-toxic. They tested the combination of two enzymes derived from micro-organisms -- prolyl-endopeptidase (PEP) and barley (EP-B2) -- to see if gluten that is treated with these enzymes, when given to celiac patients, would avoid the usual toxic effects of gluten.

Investigators performed a double blind cross-over study of 20 celiac patients who had biopsy-proven disease and had recovered from the disease on a gluten free diet. Each patient was randomized to ingest either five grams of gluten or five grams of gluten pre-treated with the enzyme treatment, daily for two weeks. Then, after participating in a wash-out period of six weeks following the conclusion of the two week treatment, patients then switched to consume the alternative gluten preparation. Each patient's gluten processing was tested via fecal fat analysis. Patients were also asked to report and record the symptoms they experienced during each phase of the trial.

Researchers found that half of the patients increased their fecal fat excretion in response to the ingestion of untreated gluten. In contrast the enzyme pre-treated gluten did not increase the fecal fat output in these patients, supporting the possibility that a combination of the two enzymes could be a potential future treatment that would allow celiac patients to eat a normal diet.

"Our evidence supports the concept that these enzymes can break down gluten and by so doing "detoxify" it said Peter Watson, MD FRCP, Belfast Hospitals Trust, Belfast, United Kingdom. "A treatment of this kind would finally allow those with celiac disease to enjoy social occasions and not worry when they are in situations where they cannot control the preparation of food."

The study was limited by the fact that not all patients are sensitive to five grams of gluten per day; however the researchers only wanted to ask patients to ingest amounts that would show measurable results. Higher levels of gluten would likely cause patients in the trial to suffer from more severe symptoms.