“For the last thirty years, the best we could do for our patients with celiac disease was advise them to go on a gluten-free diet. Not only is complying with this diet difficult, contamination introduces gluten to many supposedly gluten-free foods. Unfortunately, a significant percentage of patients who rigorously follow the diet, will still experience symptoms. finally, several treatments being developed hold forth the prospect of better management of celiac disease and an enhanced quality of life for those who have it.” – Dr. Sunil Khurana
Celiac disease (CD) is a chronic inflammatory autoimmune disease of the small intestine. People with CD cannot tolerate gluten, a protein present in wheat, barley and rye. When they do consume gluten, their immune systems respond by damaging or destroying the villi—tiny, fingerlike protrusions lining the small intestine—which normally allow nutrients to be absorbed through the walls of the small intestine into the bloodstream. Without healthy villi, a person becomes malnourished, no matter how much food he or she consumes. Years of research have yielded insights into the physiological processes contributing to CD, which include genetic vulnerability, the gluten trigger and an unusual permeability of the intestines that allows gluten to penetrate. The new treatments in the pipeline seek to address each of these factors.
“Since gluten is the problem, one strain of research in development is striving to genetically modify gluten and remove its toxicity for people with CD,” says Dr. Sunil Khurana, director of Premier’s GI Division.
Studies show that it is possible to breed gluten proteins that do not stimulate an autoimmune response. If this approach is successful, it will be possible to introduce “detoxified” wheat into the CD diet, making it easier to enjoy well-balanced meals containing the vitamin B missing from most gluten-free grains.
“Another promising approach involves developing a therapeutic vaccine for celiac disease,” Khurana says. “It works in the same way as the therapy for desensitizing people with allergies. You start with a low dose and gradually increase it to desensitize people to the effects of the gluten.”
The vaccine will be given in multiple small doses, by injection, creating immune tolerance and preventing the damaging inflammation of CD.
On the near horizon
One of the treatments closest to becoming available, perhaps within the next five years, is a zonulin inhibitor. “Zonulin is a human protein that contributes to the intestinal damage caused by celiac disease,” Khurana explains. “Whereas the villi are normally tightly attached, exposure to zonulin (stimulated by a component in gluten) breaks them up, decreases the barrier and increases the permeability of the villi.
The zonulin inhibitors will interrupt the process and keep the gluten from getting into the cells and damaging the villi,” Khurana says. The drug, as used in current studies, is designed to be taken in pill form before a meal that includes food containing gluten. The FDA has recently approved the study of this drug in the treatment of Crohn’s disease, which is also affected by zonulin production. “A quite new and fascinating area of investigation involves a set of probiotics that contain protease,” says Khurana. “The protease enzymes will deactivate the gluten that is in the stomach, before it can reach the small intestines where it causes the damage of CD.
The probiotics, for their part, will contribute to mucosal healing in the wake of previous CD damage. These protease pills are being tested with people who have been following a gluten-free diet yet are still experiencing symptoms.” “It is true that none of these treatments are clinically available just yet,” says Khurana. “They mark a set of breakthroughs that offer real hope for people with celiac disease. At Premier Medical Group, we are involved in ongoing research trials.”