Is gluten no longer scary?
The drug for celiac disease has passed the second phase of clinical trials
Anastasia Kuznetsova, N+1
Doctors from eight countries have completed the second stage of clinical trials of a drug for the treatment of celiac disease. In patients who consumed gluten daily for six months and took the medicine, it prevented the destruction of intestinal villi and reduced inflammation. The results of the clinical trials are published in The New England Journal of Medicine (Schuppan et al., A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease).
Celiac disease is a genetically predisposed intolerance to gluten contained in rye, wheat, barley and some other cereals. It affects 0.2-2 percent of people in different countries. In patients with celiac disease, inflammation of the small intestine occurs when eating gluten. This is manifested by diarrhea, weight loss, anemia, destruction of bone tissue, constant fatigue. The molecular mechanism of celiac disease is not fully understood. It is believed that the intestinal wall enzyme transglutaminase 2 modifies gluten proteins, which are then recognized by antigen-presenting cells that activate a cascade of inflammatory reactions. This leads to atrophy of intestinal villi and hypertrophy of crypts. No drugs for the treatment of celiac disease have been registered yet, although candidates are at different stages of development. Celiac patients have to follow a lifelong gluten-free diet.
A group of scientists from eight countries led by Detlef Schuppan from the Johannes Gutenberg University of Mainz has developed the drug ZED1227 for the treatment of celiac disease, which blocks intestinal transglutaminase 2, thereby preventing the modification of gluten proteins. In the first phase of clinical trials, the drug has already shown its safety when used in humans, so scientists have started the second phase of trials. To find the right dosage of the drug, they divided 163 patients into four groups: in the first group (41 people), the drug was taken at a dosage of 10 milligrams per day, in the second group (41 people) – 50 milligrams, in the third (41 people) - 100 milligrams, and the fourth group (40 people) was given a placebo instead of the drug. The patients took the medicine before breakfast, and 30 minutes after taking it they ate cookies containing 3 grams of gluten. During the six months of the study, the patients followed their usual gluten-free diet. The researchers assessed the state of the intestine according to a duodenal biopsy: with inflammation, the number of white blood cells in it increases and the number of villi decreases, but crypts grow at the same time.
After six months of treatment, the index of the height of the villi to the depth of the crypts was calculated in patients (with celiac disease, it decreases). In the placebo group, this index decreased by 0.61 during the study, and in people who took 50 and 100 milligrams of the drug, the decrease in the index was not so significant (0.12 and 0.13, respectively). Taking 10 milligrams of the drug prevented changes in crypts and villi less effectively (the index decreased by 0.17). The researchers also calculated the number of lymphocytes per 100 epithelial cells. In the placebo group, the number of lymphocytes increased by an average of 11 percent, in the group treated with 10 milligrams of the drug by 8.3 percent, and in the group given 50 milligrams of the drug, the number of lymphocytes increased by 6.9 percent. The most effective way to prevent inflammation was a dose of 100 milligrams: the number of lymphocytes increased by only 1.5 percent.
Side effects that could relate to treatment were observed in 34 percent of patients in the group taking 10 milligrams of the drug, in 46 percent of participants in the group receiving 50 milligrams of the drug, and in 50 percent of patients in the group with the maximum dosage. At the same time, the frequency of side effects in the groups taking the drug did not differ from the frequency of side effects in the placebo group (55 percent).
Scientists concluded that doses of 50 milligrams and 100 milligrams showed the best result, but in the future longer studies will be needed that will cover more patients.
Portal "Eternal youth" http://vechnayamolodost.ru