Tolerisation therapy for coeliac disease

Posted on August 5, 2012

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The problem with a gluten free diet is that it’s hard to follow and trace amounts are everywhere, according to Leslie Williams, president of ImmunosanT. ImmunosanT is developing a tolerisation therapy for coeliac disease. People with this autoimmune disease suffer damage to their small intestines when they eat wheat, barley, rye or oats. Currently the only known treatment for coeliac disease is a strict lifelong gluten free diet. But a tolerisation therapy could make it possible for coeliacs to eat whatever they want.

Gluten refers to a group of proteins found in wheat, barley and rye. During digestion gluten is broken down, but some short pieces of the protein, called peptides, resist breakdown. It is these fragments that cause an immune response in coeliac patients. This leads to T-cells from the patient’s own immune system attacking the finger-shaped villi in their small intestines. The damage causes a variety of bowel symptoms, and makes it difficult for patients to absorb nutrients from food. In the long term untreated coeliac patients risk osteoporosis and certain bowel cancers.

Dr Bob Anderson, a researcher at the Walter and Eliza Hall Institute in Melbourne, has discovered that just three peptides from gluten cause most of the immune reaction. Anderson’s team collected T-cells from coeliacs after they had eaten food containing gluten. They tested these cells for a reaction against gluten peptides. They used a library of 16 000 unique peptides derived from gluten proteins from wheat, barley and rye. Amazingly, they found that just three of these peptides were enough to produce 90% of the response that the T-cells made to the complete gluten proteins from these grains.

How the immune system responds to gluten peptides

Diagram showing how gluten peptides enter the cells lining the small bowel and are recognised by T-Cells from the immune system. Image source: http://www.immusant.com/technology/

Using these three petides, Anderson is working with ImmunosanT to create a tolerisation therapy for coeliac disease. This would involve injections of tiny doses of the gluten peptides, less than 1/1000th of the quantity of gluten that causes bowel damage. This would be enough for the immune system to recognise, but not enough for it to respond to. The immune system should learn from this exposure that it doesn’t need to react to gluten, eventually becoming tolerant to it.

The first clinical trial of the therapeutic vaccine showed that the peptides are safe, and do target gluten-responsive T-cells. Further clinical trials will determine what dose of the treatment would be used and how often. Weekly injections would probably be used in the induction phase, followed by a maintenance phase with injections every month or so. The trials should also determine whether the medication can induce tolerance and whether the patients can go back to eating a normal diet, Williams explains.

Depending on the outcomes of the upcoming clinical trials, the tolerisation therapy could be marketed around 2016. The aim is to allow coeliacs to eat what they like, and protect them from the bowel damage associated with sporadic exposure to gluten on a gluten free diet. Williams also hopes that understanding coeliac disease will aid research in treating other autoimmune diseases.

Thank you to Leslie Williams for agreeing to be interviewed across time zones.

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