They identify a molecule that could be used to treat celiac disease with a pill

Stock image of a supermarket. / C7

Spanish researchers decipher the mechanism of action and structure of Neprosin, key to developing a treatment against this pathology

CANARY ISLANDS7 The Gran Canarian palms

A study by the Institute of Molecular Biology of Barcelona (IBMB-CSIC) has identified a molecule that could counteract those that cause celiac disease. An autoimmune disease that is triggered in response to the ingestion of gluten and that affects more than 22,000 canaries, not counting those who do not know they have it.

The discovered molecule is called
neprosin, as announced by SINC, the scientific news agency of the Spanish Foundation for Science and Technology. It is found naturally in the digestive fluid of the carnivorous plant
Nepenthes venrata and could be key to a possible treatment, now non-existent.

The authors explain that the work is a milestone even for being administered orally in a similar way to the lactase tablets that people who are lactose intolerant take.

In the Canary Islands there are more than 22,000 celiacs, around 1.5% of the population. Despite this, 75% of Canarian celiacs would be undiagnosed

What is celiac disease?

It is an inflammatory response of the intestine triggered by a series of proteins found in cereals. When they 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-merwhich is a fragment of alpha-gliadin, a wheat glycoprotein.

The 33-mer is
able to resist gastric acids from the stomach, reach the small intestine and, once there, cross the intestinal mucosa. In the case of people with celiac disease, this peptide binds with particular ease to an immune system receptor (the human leukocyte antigen or HLA), which triggers an autoimmune and inflammatory response that causes a whole series of characteristic manifestations of the disease.

The results show thate neprosin can degrade the 33-mer peptide before it reaches the intestinewhich could avoid that answer.

Neprosin molecule structure. /

C7

The role of neprosin

The scientists' work, explains SINC, has been to analyze both the characteristics and the mechanism of action of neprosin, obtained by means of cultures that recombine human cells. They have also verified its efficacy in degrading both the 33-mer peptide and gliadin in the stomach.

Such a treatment should contain a molecule capable of breaking down toxic peptides and
be gut-friendlybe efficient enough to break down a fair amount of toxic peptides at reasonable doses, and should be active before passing into the gut, the researchers say.

“We have been able to verify that neprosin has enormous potential as a medicine, since it is much
more active in extreme conditions of digestion in the stomach than other candidate proteolytic enzymes currently being studied for their therapeutic application”, points out F. Xavier Gomis-Rüth.

"We are now going to carry out 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.

For his part, Francisco José Pérez Cano, a researcher at the University of Barcelona and another of the authors, comments that "33-mer is the most toxic peptide of those generated from gliadin and it remains to be seen whether its eradication it would be enough to eliminate the pathophysiological manifestations and responses of celiac disease».

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