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What is neprosin, the molecule that could be used to treat celiac disease with a pill

Celiac disease is a multisystemic condition that has an autoimmune basis and is caused by gluten and associated prolamins. "It is characterized by the presence of a variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, HLA DQ2 or DQ8 haplotypes, and enteropathy," they detail in the Federation of Celiac Associations of Spain.

The main treatment is a diet without products containing gluten, such as all those made with wheat. Now, a team of researchers from the CSIC has shown that a molecule called neprosin may be capable of degrading the gliadin protein and the 33-mer peptide, the main triggers of the disease.

How does this molecule work?

As stated in the statement, the work has been led by scientists from the Barcelona Institute of Molecular Biology (IBMB-CSIC), who have identified a molecule capable of "counteracting the effect of the toxic peptides that cause celiac disease" and which is found naturally in "the digestive fluid of the carnivorous plant 'Nepenthes ventrata'".

The research, which has been published in the journal Nature, has managed to decipher the mechanism of action of neprosin, its characteristics, and structure for the possible treatment of celiac disease.

This disease is caused by various proteins "rich in prolamins found in cereals". When digested in the stomach, "they break down into smaller ones (peptides) that can be toxic." Among the peptides, the 33-mer is a fragment of alpha-gliadin, a wheat prolamin, which resists gastric acids and reaches the small intestine to cross the intestinal mucosa.

"In the case of people with celiac disease, the 33-mer binds with particular ease to an immune system receptor (the human leukocyte antigen or HLA), which triggers an autoimmune and inflammatory response," they explain from the CSIC.

Degrade 33-mer before reaching the intestine

In this sense, the research showed that neprosin can degrade this peptide before it reaches the intestine, thus preventing the autoimmune inflammatory response.

In addition, the researchers have discovered the three-dimensional structure and the chemical mechanism of action of this molecule to discover its characteristics, such as thermal stability, pH profile, and its latency period, among others. "These factors are very important for a possible development of the prevention or treatment, until now non-existent, of the disease", they indicate.

"A promising route are molecules that destroy toxic peptides, and that can be administered orally, in a similar way to the lactase tablets that people who are lactose intolerant take," they detail.

They will now carry out specific trials to verify the potential of this molecule before moving on to clinical trials. "Neprosin has enormous potential to be developed as a medicine, since it is much more active in the extreme conditions of digestion in the stomach than other candidate proteolytic enzymes currently under study, collectively called glutenases", concludes the CSIC researcher, F Xavier Gomis-Rüth.

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