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Oral proteases: a new approach to managing coeliac disease
  1. Nadine Cerf-Bensussan1,
  2. Tamara Matysiak-Budnik1,
  3. Christophe Cellier2,
  4. Martine Heyman1
  1. 1INSERM U793, Paris, France
  2. 2AP-HP, Hôpital Européen Georges Pompidou, Department of Gastroenterology, Paris, France
  1. Correspondence to:
    Dr Nadine Cerf-Bensussan
    INSERM U793, Faculté de Médecine René Descartes, 156 rue de Vaugirard, 75730 Paris Cedex 15, France; cerf{at}


A life-long but constraining gluten-free diet is the only treatment currently available for coeliac disease. The human gastrointestinal tract does not possess the enzymatic equipment to efficiently cleave the gluten-derived proline-rich peptides driving the abnormal immune intestinal response in patients with coeliac disease. Oral therapy by exogenous prolylendopeptidases able to digest ingested gluten was therefore propounded as an alternative treatment to the diet. The feasibility of this approach is discussed by reviewing recent data on the intestinal transport of gliadin peptides, properties of available enzymes and preliminary clinical assays. Development of new enzymes or enzymatic cocktails offers potentially more potent therapeutic tools that, however, need meticulous evaluation based on clinical, biological and histological criteria.

  • PEP, prolylendopeptidase
  • tTG, tissue transglutaminase 2

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  • Published Online First 1 September 2006

  • Competing interests: None declared.

  • NC-B, MH and CC are supported by INSERM, AP-HP Paris, Université Paris Descartes and La Fondation Princesse Grace. TM-B is supported by a fellowship from AFDIAG (Association Française des Intolérants au Gluten).