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A pill to breakdown harmful gliadin peptides via enzymes so that gluten can
be safely consumed with meals may not be all that practical.  This study
shows that very high concentrations of prolyl-endopeptidase for at least 3
hours are needed to completely breakdown the gliadin peptides, NOT a
condition a simple pill is likely to achieve.

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Gastroenterology Volume 129, Issue 3, Pages 786-796 (September 2005)

Limited Efficiency of Prolyl-Endopeptidase in the Detoxification of Gliadin
Peptides in Celiac Disease

Tamara Matysiak-Budnik, Celine Candalh, Christophe Cellier, Christophe
Dugave, Abdelkader Namane, Teresita Vidal-Martinez, Nadine Cerf-Bensussan,
Martine Heyman

INSERM EMI-0212, Faculte Necker-Enfants Malades, Paris, France; Hopital
Europeen Georges Pompidou, Paris, France; Laboratoire DIEP, CEA/Saclay, Gif
sur Yvette, France; Institut Pasteur, Paris, France

Background & Aims: The resistance of prolamines to digestive enzymes is
thought to be a key contributor to the pathogenesis of celiac disease by
promoting the intestinal entrance of peptides able to trigger inflammation
in at-risk individuals. Oral administration of a bacterial prolyl-
endopeptidase (PEP) therefore was proposed as a treatment for celiac
disease. To delineate the feasibility of this treatment, the effect of PEP
on gliadin peptides was assessed in vitro, and ex vivo during their
transport across intestinal biopsy specimens of active celiac disease
patients. Methods: In vitro degradation by PEP of 3H-labeled gliadin
peptides 56-88 (33-mer) and 31-49, was analyzed by radio-reverse-phase high-
performance liquid chromatography and mass spectrometry. For ex vivo
studies, PEP and 3H-peptides were added together onto the mucosal side of
duodenal biopsy specimens mounted in Ussing chambers, and peptide transport
and digestion were assessed by radio-reverse-phase high-performance liquid
chromatography. Results: Gliadin peptides were degraded partly by 20 mU/mL
PEP both in vitro and ex vivo. This concentration of PEP decreased the
amount of intact peptides 31-49 and 56-88 crossing the intestinal biopsy
specimens of celiac disease patients, but could not prevent the intestinal
passage of toxic or immunostimulatory metabolites. PEP concentrations of at
least 500 mU/mL for 3 hours were required to achieve full detoxification of
peptides and to prevent intestinal transport of active fragments.
Conclusions: 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.

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