Celiac disease is characterized by being a permanent intolerance to gluten that produces digestive alterations in those affected who consume a product that contains this protein. Now a study led by members of the Institute of Molecular Biology of Barcelona (IBMB-CSIC) and the University of Barcelona has discovered a molecule that could be used to treat celiacs.
Specifically, the research, which has been published in the journal Nature Communications, refers to the molecule called neprosin, which is found naturally in the digestive fluid of the carnivorous plant Nepenthes ventrata. This molecule has the ability to counteract the effect of toxic peptides that cause celiac disease.
This finding could be an important step for the development of a possible new treatment against this chronic autoimmune disease that occurs when affected people ingest gluten, or even traces of it. The research has analyzed the mechanism of action of the molecule, its structure, and its most relevant characteristics for celiac disease.
Neprosin degrades peptide that causes celiac disease symptoms
Celiac disease is triggered by several prolamin-rich proteins found in cereals. When they are digested in the stomach, they break down into smaller ones, called peptides, which can be toxic. Among these peptides, one of the most relevant is the 33-mer, which is a fragment of alpha-gliadin, a prolamin (plant glycoprotein) from wheat.
If the results are confirmed, celiacs could take neprosin taken orally, like the lactase tablets that people who are lactose intolerant take
The 33-mer peptide resists the gastric acids present in the stomach and is able to reach the small intestine to cross the intestinal mucosa there. In celiac patients, the 33-mer easily binds to an immune system receptor – the human leukocyte antigen or HLA – which causes an autoimmune and inflammatory response that ends up causing a whole series of symptoms characteristic of celiac disease.
With neprosin, this 33-mer peptide can be degraded before reaching the intestine, thus avoiding the autoimmune inflammatory response. In vivo tests in one type of mouse showed that the molecule was effective in killing the 33-mer peptide and gliadin, preventing symptoms of the disease.
“A promising route is molecules that destroy toxic peptides, and that can be administered orally, similar to the lactase tablets that people who are lactose intolerant take,” the researchers explain. For his part, F. Xavier Gomis-Rüth, one of the authors, concludes that “the studies we have carried out have allowed us to verify that neprosin has enormous potential to be developed as a medicine, since it is much more active in the conditions of digestion in the stomach than other candidate proteolytic enzymes currently under study, collectively called glutenases, for therapeutic application, and meets all the characteristics that are required a priori for an efficient glutenase.”
.
