A research project led by the Institute of Nutrition and Food Safety (INSA) and the Faculty of Pharmaceutical and Food Sciences of the University of Barcelona, in collaboration with the Institute of Molecular Biology of Barcelona (IBMB) of the CSIC (Consejo Superior de Investigaciones Centíficas), has successfully designed and tested a gluten-degrading molecule that could be a promising ally in the management of the autoimmune disease celiac disease. It is caused by ingesting gluten and other prolamins found in cereals.
Currently, there is a complete lack of treatment options other than a gluten-free diet, and maintaining a gluten-free diet is difficult in Western societies whose diets rely heavily on wheat products.
The big advance is that this molecule is effective at very low concentrations and at pH 2 (the pH of the stomach). This is a condition that has not been efficiently achieved until now with molecules currently available or in development. Some of them are sold as dietary supplements, but they are not effective replacements for a gluten-free diet.
The study was published in the journal EMBO molecular medicine The study, led by researchers Francisco J. Pérez-Cano (INSA-UB) and F. Co-lead authors are Marina Girbal-González and Arturo Rodríguez-Banqueri (INSA-UB and IBMB-CSIC, respectively).
Teams from the Food Science Institute (CSIC-UAM), the University of Salzburg (Austria) and the Technical University of Munich (Germany) also participated.
Combating the “triggers” of celiac disease
The trigger for celiac disease is prolamin, a protein found in the most common grains in our diet, such as wheat gluten. When these are digested in the stomach, they are broken down into smaller fragments (peptides). Some of these are toxic, such as gluten immunogenic peptide (GIP), which survives stomach acid and reaches the small intestine. One of the most immunogenic of these is the “33-mer,” a highly immunogenic fragment of α-gliadin from wheat gluten.
This poses a problem for people with celiac disease. This is because, once in the small intestine, 33mer and other GIPs bind particularly easily to receptors of the immune system (human leukocyte antigens, or HLA), triggering an inflammatory autoimmune response that causes the characteristic symptoms of the disease.
Four years ago, the Protein Degradation Group at IBMB-CSIC, led by F. Xavier Gomis Roos, described in the following article: nature communications Nephrosin – a molecule naturally found in the digestive juices of carnivorous plants Nepenthes — Based on the results of David Schriemer’s group at the University of Alberta in Canada, it was possible to sever the GIP.
In collaboration with the Autoimmunity, Immunonutrition, and Tolerance Group at UB’s School of Pharmacy and Food Sciences, led by Professor Francisco José Pérez-Cano, they demonstrated that nephrosin can degrade 33-mer peptides and other GIPs before they reach the intestine, thereby potentially preventing this autoimmune inflammatory response.
Designed using molecular engineering
In this study, the team designed and tested a molecule based on nephrosin. named ceriacasethis new molecule exhibits maximum activity at gastric pH in the stomach and, in synergy with pepsin in the digestive system, degrades grain GIP and wheat gliadin before entering the duodenum.
There are other proteases that are collectively called proteases. glutenaseAlthough they break down gluten, they are not fully active at pH 2 (stomach pH), but rather at pH 7 (duodenal pH), when the bolus has already left the stomach. Therefore, it is necessary to increase the dose to a level where it can no longer be used therapeutically. ”
F. Xavier Gomis Roos, IMB – Research Professor, Institute of Molecular Biology, Barcelona
The team tested the molecule alive We use a mouse model developed by the University of Chicago. This is currently the model that most accurately reproduces celiac disease. The results showed that ceriacase is effective at very low doses and can reduce disease symptoms in mice fed gluten, even when gluten intake is high. “There was a reduction in intestinal atrophy, inflammation, antibody responses, dysbiosis, or changes in the composition of the microbiome,” Perez-Cano says. “Furthermore, immune regulatory markers were restored to normal levels, as were microbial metabolic pathways.”
These results indicate that ceriacase, a molecule that is stable within the gastric environment, may be an adjunctive therapeutic candidate to support a gluten-free diet.
Another advantage of ceriacase is that it becomes inactive once it reaches the duodenum. “Once it has performed its function, there is no need to keep it active so as not to interfere with other proteins in the body,” Gomis-Ruth added.
The molecule and its potential applications have been patented, and the team is taking the first steps to form a spin-off company and take development to a more advanced stage.
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Reference magazines:
Gilbar Gonzalez, M. others (2026) Targeted enzyme therapy for celiac disease. EMBO molecular medicine. DOI:10.1038/s44321-026-00430-8. https://link.springer.com/article/10.1038/s44321-026-00430-8.
