A Lab-Engineered Molecule Named Celiacase Could Change How Celiac Disease Is Managed

For the roughly 70 million people worldwide living with celiac disease, the gluten-free diet has been the only recognized treatment for decades. That picture may be beginning to change. A study published in EMBO Molecular Medicine in May 2026 describes a newly engineered molecule called celiacase that shows real promise as a supplemental therapy, able to break down the most immunologically dangerous gluten fragments while they are still in the stomach, before they ever reach the intestine.

Celiac disease is an autoimmune condition in which the immune system reacts to prolamins, proteins found in wheat, barley, and rye. When these proteins are digested, they are broken into smaller fragments. Some of those fragments, called gluten immunogenic peptides (GIPs), are resistant to stomach acid and make it to the small intestine intact. Among them, the "33-mer," a fragment of alpha-gliadin from wheat gluten, is especially problematic. Once in the small intestine, the 33-mer and similar GIPs bind readily to HLA receptors on immune cells, triggering the inflammatory autoimmune response that damages the intestinal lining and causes the characteristic symptoms of celiac disease: digestive distress, nutrient malabsorption, fatigue, and, if sustained, longer-term complications.

The research team at the Institute of Molecular Biology of Barcelona (IBMB-CSIC) and the Institute for Research in Nutrition and Food Safety (INSA) at the University of Barcelona built celiacase on a foundation laid several years earlier. In prior work, they showed that neprosin, a naturally occurring enzyme found in the digestive juice of the carnivorous plant Nepenthes ventrata, was capable of cleaving GIPs. The scientific challenge was that other enzymes used for this purpose, broadly called glutenases, are only active at pH 7, the neutral environment of the duodenum. By then, food has already left the stomach, meaning the harmful peptides have had an opportunity to cause damage. The team set out to engineer a molecule that would work at pH 2, the highly acidic environment of the stomach itself.

Celiacase achieves exactly that. Working at gastric pH and in synergy with pepsin, the stomach's natural digestive enzyme, celiacase breaks down the 33-mer and other GIPs effectively at very low concentrations. Tests using a mouse model of celiac disease developed at the University of Chicago, currently considered the most accurate animal model available, showed that celiacase reduced intestinal atrophy, inflammation, the antibody response, and dysbiosis (an imbalance in gut microbiome composition), even when the mice consumed high amounts of gluten. Immunoregulatory markers and healthy microbial metabolic pathways were restored to normal levels. Celiacase also has a built-in safety feature: once it passes into the duodenum, the molecule is no longer active, so it does not interfere with other proteins elsewhere in the body.

The study was published ahead of International Coeliac Disease Day on May 16, with the molecule and its potential applications already protected by patent. The research team is taking early steps to establish a spin-off company and advance development toward clinical trials. The goal is not to replace the gluten-free diet but to provide people with celiac disease a supplemental tool that reduces the consequence of inadvertent gluten exposure, a challenge that remains very real in everyday life.