Celiac Disease: A Challenging Disease for Pharmaceutical Scientists
- 1.1k Downloads
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.
KEY WORDSadjuvant therapy autoimmune disorder celiac sprue drug formulation polymeric drug
human leukocyte antigen
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.
- 1.Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PHR, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2012. doi: 10.1136/gutjnl-2011-301346.
- 28.Barratt SM, Leeds JS, Sanders DS. Quality of life in coeliac disease is determined by perceived degree of difficulty adhering to a gluten-free diet, not the level of dietary adherence ultimately achieved. J Gastrointest Liver Dis. 2011;20(3):241–5.Google Scholar
- 33.Brown GJ, Daveson J, Marjason JK, Ffrench RA, Smith D, Sullivan M, et al. A phase I study to determine safety, tolerability and bioactivity of Nexvax2® in HLA DQ2+ volunteers with celiac disease following a long-term, strict gluten-free diet. Gastroenterology. 2011;140(5):S-437–8.CrossRefGoogle Scholar
- 45.Adelman DC. Gluten degradation by ALV003, a novel drug in development for coeliac disease. 26th AOECS general assembly, international coeliac disease scientific conference—better life for coeliacs. 2012. 6.-9.09.2012, Helsinki, Finland (2012).Google Scholar
- 50.Robic S. Alvine Pharmaceuticals Inc, USA, assignee. PEGylated Glutenase Polypeptides. Patent WO2007047303A2. 2007.Google Scholar
- 56.Rauhavirta T, Oittinen M, Kivistö R, Männistö P, Garcia-Horsman J, Wang Z, et al. Are transglutaminase 2 inhibitors able to reduce gliadin-induced toxicity related to celiac disease? A proof-of-concept study. J Clin Immunol. doi: 10.1007/s10875-012-9745-5.
- 58.Hils M, Weber J, Buechold C, Pasternack R. Selective blockers of tissue transglutaminase for coeliac disease therapy. 26th AOECS general assembly, international coeliac disease scientific conference—better life for coeliacs. 2012. 6.-9.09.2012, Helsinki, Finland (2012).Google Scholar