Prolyl-Endopeptidase Enzymes (PEP) Not Practical in the Detoxification of Gliadin Peptides in Celiac Disease

Celiac.com 09/14/2005 - Researchers have long thought that the resistance of gliadin prolamines to digestive enzymes is a primary contributor to celiac disease—which leads to the intestinal permeability and inflammation in those who are at risk. Taking prolyl-endopeptidase enzymes (PEP) orally has been proposed and explored as a possible treatment for celiac disease (including extensive research done at Stanford Universitys Celiac Sprue Research Foundation – CSRF). In an effort to determine the feasibility of such a treatment, researchers in France conducted both in vitro (outside a living organism) and ex vivo—using biopsy specimens of active celiac disease patients—studies on the effects of PEP on gliadin peptides.

The results indicate that in both in vitro and ex vivo studies the gliadin peptides were only partly degraded by 20 mu/ml of PEP. This concentration of PEP decreased the quantity of intact gliadin peptides (31-49 and 56-88) that crossed the intestinal biopsy specimens, but did not prevent the intestinal passage of toxic or immunostimulatory metabolites—for this the researchers determined that PEP concentrations of at least 500 mu/ml for at least 3 hours was required to achieve full detoxification of gliadin peptides, and thus prevent intestinal transport of active fragments—unfortunately this finding virtually eliminates PEP as a possible treatment option for those with celiac disease.

The researchers conclude optimistically, however: "After prolonged exposure to high concentrations of PEP, the amount of immunostimulatory gliadin peptides reaching the local immune system in celiac patients is decreased. These results provide a basis to establish whether such conditions are achievable in vivo (in living organisms)."