The CSIC identifies a molecule that could be used to treat celiac disease – Diario Enfermero

EUROPA PRESS.- A study led by scientists from the Molecular Biology Institute of Barcelona, ​​of the Higher Council for Scientific Research (IBMB-CSIC), has identified a molecule, neprosin, which could be used to treat celiac disease orally, similar to the lactase tablets taken by people who are lactose intolerant. Specifically, neprosin, which is found naturally in the digestive fluid of the carnivorous plant ‘Nepenthes ventrata’, could counteract the effect of the toxic peptides that cause this chronic autoimmune disease that is triggered in response to gluten intake. As revealed by the work, published in Nature Communications, neprosin is a “promising” treatment option for celiac disease. The authors have deciphered the mechanism of action of the molecule, its structure, as well as its most relevant characteristics. Celiac disease is triggered by various prolamin-rich proteins found in cereals. When these proteins are digested in the stomach, they break down into smaller ones (peptides) that 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. The 33-mer peptide is able to resist the gastric acids of the stomach and reach the small intestine and, once there, it crosses 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 that ends up causing a whole series of characteristic manifestations of celiac disease. the illness. The results show that neprosin can degrade the 33-mer peptide before it reaches the intestine, which could prevent this inflammatory autoimmune response. Scientists have grown recombinant human cell cultures to get enough neprosin. They have identified and determined the mechanism of action of neprosin, as well as its ability to destroy gliadin and the 33-mer peptide. ‘In vivo’ experiments in a murine model show that the molecule is effective in degrading both structures in the stomach. They have also resolved the three-dimensional structure and the chemical mechanism of action of neprosin and have established characteristics such as its thermal stability, its 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. “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 scientists explain. Gut-friendly treatment Such a treatment should contain a molecule capable of breaking down toxic peptides and be gut-friendly; it should be efficient enough to degrade a fair amount of toxic peptides at reasonable doses; and it should be active before passing into the intestine, the researchers say. “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 extreme conditions of digestion in the stomach than other candidate proteolytic enzymes currently under study, collectively called glutenases, for their therapeutic application, and meets all the characteristics that are required a priori for an efficient glutenase”, points out CSIC researcher F. Xavier Gomis-Rüth. “We are now going to move on to more specific tests to verify this potential before moving on to clinical trials and working with mutant molecules that may be even more efficient,” he adds. The 33-mer peptide is one of the main causes of celiac disease, since it is generated by the degradation of a prolamin from wheat, one of the most widespread cereals on the market. Wheat gluten is easy to find in countless food, pharmaceutical and cosmetic products. “The 33-mer is the most toxic peptide of those generated from gliadin and it remains to be seen whether its eradication would suffice to eliminate the manifestations and pathophysiological responses of celiac disease,” adds Francisco José Pérez Cano, a researcher at the University from Barcelona.