According to the University of Chicago Celiac Disease Center, over 3 million people in the United States currently suffer from celiac disease, an intestinal inflammatory disease with auto-immune features. The ingestion of gluten triggers immune system responses in the human body, generally causing severe gastrointestinal pain, as well as other long-term problems including malnutrition and fatigue. Although these symptoms and further intestinal damage can be avoided by maintaining a strict gluten-free diet, this can be difficult and present a financial burden. Because of this, many scientists are searching for treatment methods for celiac disease. Significant advances have been made in this field recently, including an intestinal medicine, a vaccine, and a microbial therapeutic approach.
The immune system of people with celiac disease is triggered when incompletely-digested gluten peptides go between the cells of the lamina propria in the small intestine or pass through the space between the epithelial cells. This immune response results in the disassembly of the tight junction in the intestine and creates an opening. A new drug called larazotide acetate supposedly works to prevent this opening. A study to test the efficacy of this medicine was done on adults with biopsy-proven celiac disease. The participants who received the active larazotide acetate and ingested gluten reported less severe symptoms than those receiving the placebo study medication while on the gluten challenge. “As this is the first published clinical trial detailing results of a clinical trial for a medication designed to prevent toxicity related to gluten exposure, this is a landmark in celiac disease research,” said Daniel Leffler, MD, MS, Director of Clinical Research at the Celiac Center at Beth Israel Deaconess Medical Center.
The therapeutic vaccine Nexvax2 takes a different approach; its goal is not only to prevent the immune response but also to restore celiac patients’ immune tolerance to gluten and return intestinal health, allowing patients to eat a normal diet. Nexvax 2 combines three proprietary peptides that elicit an immune response in patients with celiac disease with the immune recognition gene HLA-DQ2. The vaccine is designed to reprogram gluten-specific T cells triggered by the patient’s immune response. “We are kicking-off a robust clinical program that we hope demonstrates Nexvax2 dramatically reduces the body’s immune response to dietary gluten so patients can resume a normal diet and return to good health,” said Patrick H. Griffin, M.D., Chief Medical Officer of ImmusanT. Studies in Australia and New Zealand have evaluated Nexvax2 for the induction of gluten tolerance in patients on a gluten-free diet. An additional study is being conducted in the U.S. to determine the safety, tolerability and pharmacokinetic profile of Nexvax2 in patients whose celiac disease is well-controlled by a gluten-free diet.
Another therapeutic approach does not attempt to change the human immune system; instead it uses microorganisms to break down gluten proteins in the digestive system. The most favorable source for gluten-degrading enzymes is the microbiome colonizing the human gastro-intestinal tract, such as gluten-degrading bacteria that naturally reside in the oral cavity. In an early study, gluten-degrading microorganisms were isolated, identified, and functionally characterized with regard to their degradation capabilities. These observations suggest that Rothia bacteria may contribute to the digestive processing of immunogenic gluten proteins. From a therapeutic perspective, these Rothia enzymes have a few major differences compared to the major glutenase enzymes that are currently being tested in clinical trials. Most notably, the enzyme source is a resident human body-associated oral commensal bacterium and has a wide pH activity range. However the in vivo usefulness of these enzymes to treat celiac disease is yet to be evaluated.
Although most of these treatment methods are in pre-clinical or early clinical trials and unlikely to be available for public use in the near future, research in the field of celiac disease is increasing and hopefully will soon offer a form of relief to those suffering from the disease.
Blog