Understanding Celiac Disease

Celiac disease is a T-cell mediated chronic inflammatory disorder predominantly affecting the bowel. In celiac patients, the ingestion of gluten-containing foods, such as those containing wheat, barley and rye, results in inflammation of the small intestinal mucosa and the disruption of its normal architecture. Celiac disease is one of the most common genetically-associated diseases. According to the journal Gastroenterology, screening studies looking at celiac-specific antibodies have shown that one to three percent of the general population in Europe and the U.S. will be affected by the disease and that for each currently diagnosed case of celiac disease, there may be between three to seven undiagnosed cases.

There is a wide spectrum of symptoms associated with celiac disease - some individuals suffer severe diarrhea, weight loss, abdominal pain and malnutrition, whereas others present with much milder symptoms. In addition, the disease can affect the skin, bones, reproductive system and the central nervous system. Currently the only effective treatment for the disease is the lifelong adherence to a gluten-free diet.

Untreated, celiac disease is associated with a mortality rate that exceeds that of the general population by approximately two to four percent, according to The Lancet. This is mainly due to the increased incidence of cancer (especially T-cell lymphoma) in this patient population. Maintenance of a strict long-standing gluten-free diet substantially reduces this risk. In addition, untreated celiac disease can result in osteoporosis, infertility and an increased risk of autoimmune diseases such as diabetes mellitus, thyroid disease and Addison's disease.

Patients with celiac disease are usually initially treated by gastroenterologists or pediatricians in the hospital setting and subsequently by general practitioners in the community. Strict maintenance of a diet entirely devoid of gluten is both very difficult for patients to achieve and also expensive. Full healing of the bowel mucosa is often not achieved.

ChemoCentryx has initiated a randomized, double-blind, placebo-controlled, Phase II clinical trial to test Traficet-EN™ in the treatment of patients with celiac disease. It is known that the trafficking of T-cells to the small intestinal mucosa is controlled by the chemokine receptor CCR9 and its ligand CCL25. CCR9 positive T-cells are thought to play a key role in the pathological response triggered by gluten exposure. The use of a CCR9 antagonist to inhibit T-cell homing to the digestive tract may provide a promising therapeutic strategy in the treatment of celiac disease.

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