Transglutaminase as a therapeutic target for celiac disease

Abstract

Introduction: The only current treatment for celiac disease is a strict gluten-free diet. The ubiquitous presence of gluten in groceries, however, makes the diet burdensome and difficult to maintain, and alternative treatment options are thus needed. Here, the important role of transglutaminase 2 (TG2) in the pathogenesis of celiac disease makes it an attractive target for drug development.

Areas covered: The present paper gives an overview of TG2 and addresses its significance in the pathogenesis of celiac disease. Moreover, the article summarizes preclinical studies performed with TG2 inhibitors and scrutinizes issues related to this therapeutic approach.

Expert opinion: Activation of TG2 in the intestinal mucosa is central in celiac disease pathogenesis and researchers have therefore suggested TG2 inhibitors as a potential therapeutic approach. However, a prerequisite for such a drug is that it should be specific for TG2 and not affect the activity of other members of the transglutaminase family. Such compounds have already been introduced and tested in vitro, but a major obstacle to further development is the lack of a well-defined animal model for celiac disease. Nonetheless, with encouraging results in preclinical studies clinical trials with TG2 inhibitors are eagerly awaited.

Keywords:

• celiac disease
• drug
• gluten
• inhibitor
• small-bowel
• transglutaminase

Declaration of interest

The authors were supported by The Celiac Disease Study Group has been financially supported by the Academy of Finland, the Sigrid Juselius Foundation, the Competitive State Research Financing of the Expert Area of Tampere University Hospital (grants 9R034 and 9R018) and Seinäjoki Central Hospital (VTR16), The Finnish Medical Foundation and the Foundation for Pediatric Research. K Kurppa has participated in a Phase II clinical drug trial (Alvine Pharmaceuticals, Inc.) and a pilot study (BioLineRX. Ltd). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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