Celiac Disease: A Challenging Disease for Pharmaceutical Scientists
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PERSPECTIVE
Celiac Disease: A Challenging Disease for Pharmaceutical Scientists Simon Matoori & Gregor Fuhrmann & Jean-Christophe Leroux
Received: 23 September 2012 / Accepted: 30 November 2012 / Published online: 11 December 2012 # Springer Science+Business Media New York 2012
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 glutenfree 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. S. Matoori Department of Chemistry and Applied Biosciences ETH Zurich Institute of Pharmaceutical Sciences Wolfgang-Pauli-Str. 10, HCI 8093 Zurich, Switzerland G. Fuhrmann Department of Chemistry and Applied Biosciences, ETH Zurich Institute of Pharmaceutical Sciences Wolfgang-Pauli-Str. 10, HCI J 398 8093 Zurich, Switzerland J.-C. Leroux (*) Department of Chemistry and Applied Biosciences, ETH Zurich Institute of Pharmaceutical Sciences Wolfgang-Pauli-Str. 10, HCI H 301 8093 Zurich, Switzerland e-mail: [email protected]
KEY WORDS adjuvant therapy . autoimmune disorder . celiac sprue . drug formulation . polymeric drug 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(hydroxyethylmethacrylateco-styrene sulfonate) PEP prolyl endopeptidase TfR transferrin receptor TG2 transglutaminase 2
INTRODUCTION Celiac disease (CD) is defined as “a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals” (1). Nonetheless, CD is a systemic disease with a wide variety of clinical symptoms (2,3). A recent study based on serologic testing found a prevalence of up to 1% among the white ethnic population (4). CD prevalence has been on the rise for many decades, wi
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