In a newly published study, researchers report finding a previously unknown molecular target in celiac disease. The molecule is also linked to cystic fibrosis, suggesting there is potential for treating the disease by repurposing certain drugs to treat cystic fibrosis. The international team of researchers who worked on the study published their findings in the EMBO Journal.
About 1 in 100 people suffer from celiac disease, but the prevalence is approximately 3 times higher in patients who also suffer from cystic fibrosis. In the current study, the researchers sought to explore the basis for any link between these two diseases.
Cystic fibrosis is characterized by build-up of thick, sticky mucus in the patients’ lungs and intestine and is caused by mutations in the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR). CFTR plays an important role in keeping mucus fluid, when it malfunctions, mucus clogs up and a number of other effects occur in the lungs and other organs. These are very similar to the responses triggered by gluten in celiac patients.
The researchers studied celiac using human intestinal cell lines that are sensitive to gluten. In these models a specific peptide called P31-43 was observed to bind to CFTR and impair its function. The interaction triggers cellular stress and inflammation, suggesting CFTR plays a role in mediating gluten sensitivity in celiac patients.
When the researchers introduced a potentiator of CFTR, called VX-770 to the system, the interaction between P31-43 and CFTR was inhibited. Intestinal cells or tissue samples collected from celiac disease patients pre-incubated with VX-770 before being exposed to P31-43, peptides released from gluten did not elicit a response. The researchers also found that VX-770 could protect gluten-sensitive mice from gluten-induced symptoms.
These findings suggest that CFTR potentiators, already developed to treat cystic fibrosis, may also have potential for treating celiac disease.