The only effective and clinically relevant treatment to date is a lifelong adherence to a gluten free diet. In the absence of the gliadin proteins found in gluten, the body can completely reverse any negative effects associated with the autoimmune response to gluten. A gluten free diet involves avoiding any foods that contain wheat rye or barley (Niewinski, 2008). In the United States, oats that are not steel cut should be avoided given that they are processed with wheat, but oats themselves do not contain any gluten peptides. Mechanistically, by removing the environmental factor that induces any immune response, it is easy to see how this therapy is so effective at eliminating symptoms.
Despite this being the only relevant treatment to date, there are multiple opportunities to develop therapies that inhibit the pathogenic pathway of Celiac disease, and there are several treatments currently being researched that attempt to do just that. For example, both Larazotide acetatehave and several endopeptidases are being tested and have shown promising results in reducing symptoms of Celiac disease (Vanga, 2014). Larazotide acetate functions by modulating the integrity of tight junctions and thereby reducing the passage of gliadin through the intestinal mucosa, whereas the endopeptidases function to further digest any gliadin fragments, reducing the prevalence of any potential epitopes that could incite an immune response.
In general, there are a vast number of ways to attack this disease. Anything from oral proteases to drugs that target zonulin expression, to enzymes that inhibit the function of tissue transglutaminase, to gluten sequestering polymers that bind gliadin under gastric and intestinal conditions are being developed and undergoing tests to be clinically approved (Khosla, 2011). Speicifally, a drug cocktail called STAN1, which incorporates an oral protease, is now being developed and has reached clinical trials(Khosla, 2011). There are also a few individual oral protease drug therapies that are currently in clinical trials as well. In any event, the majority of the treatments being developed focus on either reducing the permeability of the membrane, reducing the binding ability of HLA-DQ2 or HLA-DQ8, or reducing the bodies ability to incite an immune response in the presence of gliadin (Khosla, 2011). Below is a graphic that shows the vast number of treatments that are being developed. The abbreviations used from the paper have been included in the picture.
Besides these drug treatments, there are a few more alternative therapies that have received some attention. Gluten tolerization, for example, is now in clinical trials(Khosla, 2011). This is essentially the process of introducing a peptide vaccine to reduce the bodies immune response against various epitopes of gliadin. There is currently a a prototypical vaccine, NexVax, in trials that is designed to increase the bodies resistance against multiple epitopes of gliadin(Khosla, 2011). The variety of possibly immunogenic epitopes pose a problem for this treatment, however, given that it is difficult to design a vaccine that could provide resistance to upwards of 50 epitopes.
Genetic modification to remove the immunogenic gliadin portion of the wheat plant is a more radical therapy that does not necessarily focus on the individual with the disease (Vanga, 2014). This would effectively reduce any T-stimulatory epitopes in circulation after an individual consumes wheat, and would therefore reduce any immunogenic effects. A related study in which pretreatment of flour with lactobacteria, which are capable of digesting the highly immunogenic 33-mer gliadin peptide, unfortunately, still showed enhanced permeability of the small intestine (Vanga, 2014). This is most likely due to the vast amount of epitopes in gliadin capable of inducing an immunogenic response.
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