Life is not easy for those with celiac disease.

According to a recently published report, an individual with celiac disease spends about AUD 1,650 more per year than someone who does not suffer from this disease. This extra expense can be explained away by an increase in the cost of the premium materials used in the preparation of Gluten-free foods as well as the increased costs in technologies used by the industry to ensure the safety and quality of Gluten-free products.

Complicating matters further is the fact that few restaurants are adequately prepared to cater to those suffering from celiac disease, and those that do, often employ individuals who lack the training to be able to properly identify all potential sources of gluten in food, as well as the knowledge to guarantee a gluten-free meal adequately.

Furthermore, there is substantial evidence to suggest that prompt diagnosis and adequate treatment for patients suffering from celiac disease confers significant health benefits in the short, medium, and long term. Although the primary treatment strategy for celiac disease is to adopt a diet that is entirely gluten-free, few individuals are able to successfully do so because it can be prohibitively expensive, highly inconvenient, and challenging to adhere to over time.

Therefore, the medical community is heavily invested in developing therapeutic strategies that can provide celiac patients with viable and effective alternative treatment options. The latest research into the fields of immunology, genetic engineering, and peptide and protein modulation have provided celiac patients from around the globe with promising advances. The latest cutting edge treatments for celiac disease focus on decreasing exposure to gluten, modifying intestinal permeability, and modulating the body’s immune response.

Today we will talk briefly about some of the promising and exciting treatments that are being developed as well as their mechanisms of action in relation to the causes and development of celiac disease.

What is Gluten and how does it cause Celiac Disease?

Celiac disease is an intestinal pathology triggered by the ingestion of gluten in genetically predisposed subjects.

Gluten is an insoluble polypeptide protein with a high content of prolamins and glutelins, found primarily in common grains such as wheat, rye, spelt and barley. When ingested, this protein causes severe and chronic inflammation in the small intestine that is mediated by the Human Leukocyte Antigen system, which is responsible for regulating the body’s immune apparatus. The subsequent immune response often triggers malabsorption of a variety of essential nutrients.

Clinical manifestations of the disease vary according to the age of the patients. For example, in pediatric patients, the disease is characterised by the appearance of diarrhea, abdominal distention and a predominant retardation of healthy growth. In adults, however, the symptomatology is much more atypical and usually presents vastly different symptoms such as anemia, early-onset osteoporosis, and alterations to intestinal transit.

Although celiac disease has a relatively small prevalence in developed countries, typically around 1% of the population, it is estimated that there is a significant proportion of the population who may not be correctly diagnosed by the traditional screening procedures.

Currently, the only effective treatment for celiac disease is the strict consumption of a gluten-free diet. However, it has been repeatedly shown that recovery is far from immediate, and there is even a significant proportion of celiac patients, typically between 30% and 50%, with persistent intestinal lesions and recurrent symptoms despite a correct diagnosis and its subsequent treatment.

The strict monitoring of patients with non-responsive celiac disease entails an enormous personal sacrifice which in itself invites hardship in the patient’s psychological and social spheres.  Additionally, amongst patients who are unresponsive to gluten-free diets, there is an increased risk of developing potentially life-threatening complications such as T-cell lymphoma.

Here are some of the most promising future therapies for the treatment of celiac disease:

Therapies Based on Gluten Modification

Genetically Modified Wheat Grains And Pre-Treated Flours: The current hypothesis behind these therapies boils down to the belief that reducing the gluten content of dietary cereals will significantly decrease the outcome of celiac disease across the board.

Unlike ancestral wheat strains such as Tritordeum or Triticum, the wheat strains currently used in agriculture are considered significantly more immunogenic, meaning that they are more prone to invoking an immune response in the body.

Thanks to advancements in genetic engineering, we now have wheat varieties that have significantly reduced levels, and in some cases are entirely devoid, of immunogenic gluten peptides. Unfortunately, these wheat varieties are difficult to grow and cultivate.

Modern genetic engineers use the splicing of RNA to silence gluten genes that contain peptides for celiac disease in wheat variants with a reduced content of immunogenic peptides. Some of these strains are over thousands of years old, and have been shown to confer immunogenicity, and also to have a lower proportion of glutelins.

Furthermore, Psyllium gliadin has recently been studied as a possible replacement for gluten because it has minimal effects on the smell or texture of wheat while retaining most of its cooking properties. Bread made with psyllium was highly rated both by celiac and non-celiac patients for its soft texture and its pleasant taste.

Other studies have also evaluated the genetic modification of wheat through the elimination of critical gliadin genes. Specifically, the deletion of the a-gliadin locus on modern strains of wheat produced a decrease in the stimulation of the patient’s immune response without significant alterations to the cereal’s cooking properties.

On the other hand, the use of different probiotic organisms, such as lactobacillus, is being considered as a promising therapeutic measure in the fight against celiac disease. Lactobacilli have special enzymes that when added to the dough for fermentation are able to hydrolysegluten peptides rich in glutamine and proline, including the highly immunogenic gliadin peptide.

Other studies have focused on using a protease that degrades gluten during the fermentation of wheat. Bread made from flours that have been previously treated with these proteases contain significantly lower levels of glutamines and gliadins.

Intraluminal Therapies

Gluten-Binding Polymers: the use of polymeric resin to sequester intraluminal gliadin has been suggested as an effective strategy to prevent toxic gluten peptides from gaining access to the intestinal mucosa. In Vitro, studies have shown that this polymer is able to efficiently trap specific gliadin molecules and thus prevent their digestion and subsequent transformation into immunogenic proteins. As a result, the patient experiences a significant reduction in visible intestinal damage. This procedure requires further study before it can be accepted as a viable therapeutic option for several reasons. For example, the polymer lacks a specificity towards gliadin and thus it is possible that it binds to other nutrients.

Gluten-Neutralising Antibodies: Immunoglobulin G antibodies can be administered orally, which can bind specifically to intraluminal antigens and inhibit their metabolic action. So far, these antibodies have been extracted from cow colostrum, and more recently from egg yolks rich in Immunoglobulin Y antibodies. Gluten-Neutralising Antibody therapy can be particularly useful on celiac patients with mild to moderate symptoms. These antibodies can be safely labelled and categorised as nutritional supplements and used as adjuvant therapy when consuming gluten-rich foods sporadically.

Immunomodulation and Gluten Tolerance

Helminth Infection: A multitude of strategies conducive to the gradual desensitisation against gluten have been evaluated over the years. One of the most fascinating and controversial immunotherapeutic methods is based on the hypothesis that excessive hygiene can cause an autoimmune inflammatory response. Therefore, celiac patients are purposefully infected with parasitic hookworms in an attempt to modulate immunoregulatoryactivity and response. Further studies are needed, but the practice has proven effective against celiac disease as well as inflammatory bowel disease.

Stimulation of Intestinal Mucosal Tolerance: The stimulation of intestinal mucosal tolerance to gluten has been studied in several models of celiac disease. The specific mechanisms to induce intestinal tolerance to gluten are based on the administration of immunogenic gliadin peptides previously treated with LactococcusLactis.

Gluten Vaccine: The objective of vaccination against diseases of autoimmune origin is the stimulation of regulatory T cells with the intent of suppressing inflammation as much as possible. In celiac disease, this therapy is proposed to change the response of T cells to regulate pro-inflammatory activity when gluten is ingested. In other words, the vaccine induces a generalisedtolerance to gluten. The vaccine, developed in Australia, has passed phase 1 clinical trials and is currently in phase 2 trials where it shows great promise.

Conclusion

Because celiac disease is an autoimmune condition with a complex profile of environmental and genetic triggers, there is worldwide interest in developing effective non-dietary therapeutic options.

It is now possible to think of a future where celiac patients are able to reintegrate gluten to their daily lives. However, it is important to note that most of these medications and therapies are still very early in their development and a multitude of challenges and further testing must be dealt with before they are fully available to the general populace.

Nevertheless, the future for celiac patients has never looked brighter than it does today.