Given that the disease is mechanistically so well defined, I think future work should focus primarily on discovering novel treatments and attempting to build a more algorithmic approach to determining susceptibility. In terms of discovering novel treatments, there is a lot of talk in the field about inhibiting a variety of enzymes, modulating tight junctions, etc., but there is not as much discourse regarding the inhibition of zonulin production. As the mechanism by which gliadin induces the production of zonulin, and that the overexpression of zonulin in Celiac disease patients directly correlates with increased permeability of the small intestine and therefore all of the autoimmune effects. I think that devising small molecules designed to attack either the zonulin receptor or the CXCR3 receptor that gliadin binds to offer a unique opportunity with a relatively easy delivery system (given its potential to be oratory) as a therapy for Celiac disease.
There has also been some discourse in the literature regarding microbes in the oral cavity that are capable of digesting the gluten peptides resistant to human peptidases (Vanga, 2014). There has also been discourse about the implementation of oral peptidases to help digest gliadin further (Khosla, 2011). I think further characterizing these microbes and peptidases, and if they have any adverse effects on human health could possibly offer a unique avenue to treat Celiac disease. If either don’t have any adverse oral effects, and they are capable of efficiently degrading gliadin proteins, these microbes could have significant clinical impact. Possibly similar to fluoride supplementation, either could potentially be harnessed in something as trivial as toothpaste, so that daily application could help to further degrade gliadin peptides and reduce the amount of circulating epitopes in Celiac disease individuals, which could hopefully reduce symptoms.
I think ultimately, though, further genetic characterization of the disease and a more comprehensive understanding of the degree to which varying loci are involved in disease susceptibility is the next frontier in Celiac research. Currently, the amount of ambiguity circulating disease susceptibility in given individuals makes diagnosis, particularly in asymptomatic individuals, difficult, and delayed diagnosis can cause complications in the individual. I would argue more extensive genetic mapping data combined with in depth pedigree familial inheritance analysis needs to be continued to more rigorously define which genes in what percentage confer susceptibility to the disease. I also think better defining the parameters of the trigger event would be incredibly useful in diagnosis. Given the supposed breadth and variation of possible events, however, experiments to accurately determine this would most likely be difficult to do in humans. They would most likely need to be performed in a mouse model, where environmental conditions could be strictly controlled. The only problem with this is that mouse models do not always translate well to human systems.
Despite all this, in a matter of just ten to 15 years, Celiac disease has progressed from a life manipulating illness, to a more than manageable disease given the increase in awareness and the great expansion of the gluten free options available. I can only imagine that with the current popularity of the disease and the amount of research dedicated to finding therapies for it that in the next five to ten years, Celiac disease could evolve into a minor inconvenience at most.
Jump to other pages of Celiac disease: