Next-generation therapies for celiac disease: The gluten-targeted approaches

Wheat is one of the main foods of the human diet. It contains a protein complex, gluten, which is primarily responsible for the rheological behavior of wheat flours. However, it is gluten that triggers and maintains the enteropathy in celiac disease, a common autoimmune disorder of the small intestine. Individuals who suffer from celiac disease must follow a gluten-free diet, the only effective treatment available. Compliance to the restrictive diet is demanding and new treatment strategies for celiac disease are desired by patients and clinicians. Based on increasing knowledge of the pathogenesis of celiac disease, some gluten-targeted approaches have been devised, such as down-regulation of gliadin expression, proteolysis of immunodominant peptides, transamidation of glutamine residues and sequestering of gliadin proteins. The present work critically discusses these experimental therapies, their usefulness, and the results obtained, in order to infer what the next generation of therapies for celiac disease will be. The gluten detoxification technologies have shown promising results in clinical trials by attenuating the symptomatology associated with celiac disease. These include gluten-specific proteases, which are close to entering the market for use by patients who may have mistakenly ingested food contaminated with gluten. Although so far none of the technologies allow the safe consumption of gluten without limitations, new and promising advances have been made, thus creating positive expectations in the search for an alternative to the gluten-free diet. •New treatment strategies for celiac disease are desired by patients and clinicians.•Recent approaches showed to detoxify gluten while retaining its functionality.•Specific proteases to treat gluten are well positioned to enter in the market.•Combined approaches can be the next-generation of non-dietary therapies for CD.