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Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

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ABSTRACT

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects ~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influences the susceptibility of individuals towards CD, though environmental factors also play a role. With no pharmacological treatments available, the only option to keep CD in remission is a strict and permanent exclusion of dietary gluten. Such a gluten-free diet is difficult to maintain because of gluten’s omnipresence in food (e.g., additive in processed food). The development of adjuvant therapies which would permit the intake of small amounts of gluten would be desirable to improve the quality of life of patients on a gluten-free diet. Such therapies include gluten-degrading enzymes, polymeric binders, desensitizing vaccines, anti-inflammatory drugs, transglutaminase 2 inhibitors, and HLA-DQ2 blockers. However, many of these approaches pose pharmaceutical challenges with respect to drug formulation and stability, or application route and dosing interval. This perspective article discusses how pharmaceutical scientists may deal with these challenges and contribute to the implementation of novel therapeutic options for patients with CD.

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Abbreviations

APC:

antigen-presenting cell

CD:

celiac disease

GFD:

gluten-free diet

GI:

gastrointestinal

HLA:

human leukocyte antigen

IEL:

intraepithelial lymphocyte

IgA:

immunoglobulin A

IL-15:

interleukin-15

P(HEMA-co-SS):

poly(hydroxyethylmethacrylate-co-styrene sulfonate)

PEP:

prolyl endopeptidase

TfR:

transferrin receptor

TG2:

transglutaminase 2

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ACKNOWLEDGMENTS AND DISCLOSURES

Financial support from the Swiss National Science Foundation (310030_135732) and “IG Zöliakie der Deutschen Schweiz” is acknowledged. Dr. Marc A. Gauthier is acknowledged for his critical reading of the manuscript.

J.-C. Leroux has a consultancy agreement with BioLineRx. The remaining authors disclose no conflicts of interest.

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Authors and Affiliations

  1. Department of Chemistry and Applied Biosciences, ETH Zurich Institute of Pharmaceutical Sciences, Wolfgang-Pauli-Str. 10, HCI, 8093, Zurich, Switzerland

    Simon Matoori

  2. Department of Chemistry and Applied Biosciences, ETH Zurich, Institute of Pharmaceutical Sciences, Wolfgang-Pauli-Str. 10, HCI J 398, 8093, Zurich, Switzerland

    Gregor Fuhrmann

  3. Department of Chemistry and Applied Biosciences, ETH Zurich, Institute of Pharmaceutical Sciences, Wolfgang-Pauli-Str. 10, HCI H 301, 8093, Zurich, Switzerland

    Jean-Christophe Leroux

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Matoori, S., Fuhrmann, G. & Leroux, JC. Celiac Disease: A Challenging Disease for Pharmaceutical Scientists. Pharm Res 30, 619–626 (2013). https://doi.org/10.1007/s11095-012-0951-x

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