Celiac disease may be treated with cystic fibrosis drugs

Celiac disease is an autoimmune disorder that affects 1 in 141 people in the United States.

The condition is triggered by the consumption of gluten — a protein that can be found in wheat, barley, and rye and in foods such as bread, pasta, and baked goods.

In a person with celiac disease, consuming gluten causes the immune system to attack the mucus that lines the inside of the small intestine.

This can trigger a range of digestive symptoms, such as bloating, nausea, vomiting, chronic diarrhea, and stomach pain.

Current remedies for the disease involve avoiding gluten, but new research, published in The EMBO Journal, points to novel therapeutic targets that may soon lead to effective treatments.

The study was led by Luigi Maiuri, of the San Raffaele Scientific Institute in Milan, Italy, as well as by Valeria Raia, from the University of Naples Federico II in Italy and Guido Kroemer, from Paris Descartes University in France.

Protein key in cystic fibrosis, celiac disease

Maiuri explains the starting point of the research, noting that the prevalence of celiac disease is roughly three times higher among people with cystic fibrosis — a condition in which a thick layer of mucus builds up in the lungs and intestines.

“This co-occurrence made us wonder if there is a connection between the two diseases at the molecular level,” says Maiuri.

As the researchers explain, cystic fibrosis is caused by mutations in a gene that encodes a protein called cystic fibrosis transmembrane conductance regulator (CFTR).

CFTR is an ion transport protein that keeps the mucus fluid. When this protein is faulty, the mucus becomes sticky and cloggy.

Genetic mutations in CFTR also activate the immune system, triggering a range of reactions in the lungs and intestines.

Such changes resemble the effects of gluten in people with celiac disease, so the team set out to study the molecular chain reactions in detail, hoping to discover what was behind the similarities.

The researchers studied human cell lines from people intolerant to gluten and found that a peptide called P31-43 binds to CFTR, inhibiting its function. This resulted in cellular stress and inflammation.

The findings indicate that CFTR is crucial in gluten sensitivity.

CFTR potentiators may treat celiac disease

The researchers also identified a compound called VX-770, which can stop P31-43 from impairing CFTR’s function.

The team gave gluten-intolerant mice VX-770 and found that it prevented intestinal symptoms in the rodents.

They then replicated these results in human cell lines, finding that pre-incubation with VX-770 stopped the P31-43 peptide from triggering an immune response.

VX-770 is a CFTR potentiator — a pharmacological compound that scientists developed to treat cystic fibrosis.

The new findings suggest that CFTR potentiators may also treat celiac disease.

Maiuri, Raia, and colleagues conclude:

This study identifies CFTR as a molecular target of gluten that contributes to [celiac disease] pathogenesis, providing the scientific rationale for repurposing CFTR potentiators for the prevention or treatment of [celiac disease].”

The researchers add that “Future clinical trials must explore whether oral administration of CFTR potentiators […] may be capable [of interfering] with [celiac disease] pathogenesis, [allowing] celiac individuals to avoid autoimmune comorbidities without changing their diet.”

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