Novel Treatments for Celiac Disease: Glutenases and Beyond

Abstract

Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet. However, gluten-free dieting is restrictive, difficult to maintain and nutritionally less than optimal. The improved knowledge on celiac disease pathogenesis has enabled researchers to suggest alternative strategies to treat the disorder. The drug development poses a challenge as any novel drug for celiac disease should be simultaneously effective and as safe as the gluten-free diet. The rationale behind enzyme supplementation therapy as a future treatment option for celiac patients lies in the fact that gluten is only poorly digested by gastrointestinal proteases. Due to incomplete degradation in the gastrointestinal tract, fairly long gluten peptides enter the small-intestinal lumen and come into contact with the mucosal epithelium, and in celiac disease patients this encounter launches deleterious downstream effects. Enzyme supplement therapy using either bacterial or fungal endopeptidases or proteases from germinating cereals has been proposed to promote complete digestion of prolamins and destroy disease-inducing gluten peptides. A major advantage of these glutenases is that they work in the lumen of the small intestine and do not themselves take part in the immunological cascade of events in the lamina propria, thus being unlikely to cause harmful side effects to the host. Studies to test this rationale, e.g. with Aspergillus niger prolyl endoprotease and a combination enzyme product ALV003, are already ongoing. The development of a novel medication for celiac disease is still in its early days, and thus the conventional dietary treatment will hold its place for the time being.

Development of wheat genotypes expressing a glutamine-specific endoprotease from barley and a prolyl endopeptidase from Flavobacterium meningosepticum or Pyrococcus furiosus as a potential remedy to celiac disease

“…Metabolic studies under simulated gastrointestinal conditions showed that gluten derived from such plants contain significantly less immunogenic peptides than control plants. Together, our results propose a new way of treating celiac disease and thus underscore the commercial viability of the combination enzyme therapy (Kaukinen and Lindfors 2015). …”

The Gluten-Free Diet: Fad or Necessity?

“…Currently, following the gluten-free diet for life is the only treatment for celiac disease, although medications may become available in the future (36). The gluten-free diet involves the complete avoidance of wheat, rye, barley, and regular oats.…”

Çölyak Hastalığına Diyetetik Yaklaşım

“…Çölyak hastalarında glutensiz diyet çok iyi planlansa da uyum ile ilgili sorunlar yaşanmaktadır. Hastalarda diyete uyumsuzluk % 20-80 arasında değişmektedir (15,45). En önemli uyumsuzluk nedenlerine bakıldığında; GFD sosyal yaşamı sınırlamakta, sınırlı besin alımı, glutensiz ürünlerin tatlarının farklı ve pahalı olması, uzun süreli takiplerinin zorlukları, diyet eğitimlerinin yetersizliği ve küçük miktarda bile gluten ihtiva eden besinlerin tüketiminin klinik atakları tetiklemesi olarak sıralanabilir.…”

“…En önemli uyumsuzluk nedenlerine bakıldığında; GFD sosyal yaşamı sınırlamakta, sınırlı besin alımı, glutensiz ürünlerin tatlarının farklı ve pahalı olması, uzun süreli takiplerinin zorlukları, diyet eğitimlerinin yetersizliği ve küçük miktarda bile gluten ihtiva eden besinlerin tüketiminin klinik atakları tetiklemesi olarak sıralanabilir. Yaşam tarzı değişiklikleri hem çocuk hem de ailede oluşmadığından da diyete uyum olumsuz etkilenmektedir (45,46).…”