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  • Review Article
  • Published:

Advances in the treatment of coeliac disease: an immunopathogenic perspective

Nature Reviews Gastroenterology & Hepatology volume 11, pages 36–44 (2014)Cite this article

Subjects

Key Points

  • As the knowledge of the pathogenesis of coeliac disease has increased, new alternative treatment modes (such as detoxification of gluten) to replace the burdensome gluten-free diet have been suggested

  • Several investigational approaches exist to detoxify gluten in the lumen of the small intestine, including glutenase therapy and polymeric gluten sequestrants

  • Suggested treatment options that prevent gluten-induced effects at the intestinal epithelium include blockers of intestinal permeability and IL-15

  • Other therapeutic options (such as transglutaminase 2 inhibitors and HLA blockers) are based on the prevention of the gluten-induced immunological cascade in the lamina propria

  • Currently, the most advanced drug candidates are in phase II clinical trials

Abstract

Coeliac disease is a common and fairly well-characterized systemic disorder that mainly affects the small intestine, but also has extraintestinal manifestations. The environmental trigger (gluten derived from wheat, rye and barley), the genetic predisposition conferred by the HLA-DQ2 and HLA-DQ8 haplotypes and many steps in the disease pathogenesis are known. This knowledge has enabled researchers to suggest novel alternative treatments or adjunctive therapies to the gluten-free diet, which is currently the only available and effective treatment for the condition. This Review focuses on emerging and potential treatment strategies that are based on the current concept of the disease pathophysiology. The search for novel future treatment modes, including nonpharmacological and pharmacological approaches, is also outlined. The potential pitfalls associated with the various research avenues are also discussed.

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Figure 1: Investigational approaches that work in the lumen of the small intestine that could be used to treat coeliac disease in the future.
Figure 2: Suggested treatment options that prevent gluten-induced effects at the intestinal epithelium.
Figure 3: Therapeutic options based on prevention of immunological cascades in the lamina propria.
Figure 4: Overview of the therapeutic pipeline in coeliac disease.

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Acknowledgements

The Celiac Disease Study Group have been financially supported by the Academy of Finland, the Sigrid Juselius Foundation, the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (grant numbers 9P020 and 9P033), Elna Kaarina Savolainen's fund allocated for the development of cancer treatment, Pediatric Research Foundation and the European Commission IAPP grant TRANSCOM (Contract number PIA-GA-2010-251506).

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  1. Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, FI-33014, Finland

    Katri Kaukinen

  2. Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, University of Tampere, Tampere, FI-33014, Finland

    Katri Lindfors & Markku Mäki

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All authors contributed equally to all aspects of the manuscript.

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Correspondence to Katri Kaukinen.

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M. Mäki is a member of the Scientific Advisory Board of Alvine Pharmaceuticals, ImmusanT and Flamentera AG and is a member of the Clinical Advisory Board of BioLineRx. The other authors declare no competing interests.

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Kaukinen, K., Lindfors, K. & Mäki, M. Advances in the treatment of coeliac disease: an immunopathogenic perspective. Nat Rev Gastroenterol Hepatol 11, 36–44 (2014). https://doi.org/10.1038/nrgastro.2013.141

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