Overcoming the toxicity of gluten in coeliac disease

Diets and dietary advice are everywhere, from raw vegan to meat bingeing; people are convinced there is a causal link between certain ‘magical’ foods and health.

But much of the popular advice offered around diet is unscientific, potentially dangerous, or just totally ineffectual.

For some people however, such as those with coeliac disease, following a strict diet to avoid the disease’s trigger – gluten – is the only option to manage a serious medical condition.

Now, according to gastroenterologist and University of Melbourne Fellow Dr Jason Tye-Din, a potential new treatment for coeliac disease is in clinical trials, the result of immunological research carried out by researchers at the Walter and Eliza Hall Institute of Medical Research, an affiliate of the University of Melbourne’s Department of Medical Biology.

Because gluten is a protein found in a range of grains including wheat, barley, oats and rye, it is difficult to avoid in the diet. For people with coeliac disease, exposure to dietary gluten causes an abnormal immune reaction, resulting in inflammation that damages the small bowel and reduces the body’s ability to absorb nutrition from food.

Abdominal pain, bloating, diarrhoea, weight loss, anaemia and lethargy are very common in coeliac sufferers. Premature thinning of the bones puts people at risk of fractures and there is an increased risk of related immune diseases such as type 1 diabetes, and even some forms of cancer, such as lymphoma.

The research team is working on a new therapy called NexVax2 which would be given as a series of injections to “retrain” the immune system to tolerate gluten, and works by helping desensitise coeliac sufferers to gluten’s toxic effects, with the aim of a return to normal diet and good health.

“Coeliac disease is a serious medical condition,” says Dr Tye-Din. “Early diagnosis and treatment with complete exclusion of dietary gluten is necessary to treat symptoms and reduce the risk of the more sinister complications. This is not a fad diet.

“The good news is that a gluten-free diet can treat symptoms, heal the bowel and reduce the risk of long-term health issues,” he says, “but for this to occur the diet needs to be extremely proscriptive, and lifelong.”

Following a diet strict enough to be effective is very difficult, with the ever-present risk of accidental gluten exposure. It’s also expensive, with gluten-free products adding between $500-$1000 extra in grocery bills per year.

A small amount of gluten – as little as one hundredth of a slice of normal bread – is enough to cause damage over time. And although the small bowel will eventually heal if the diet is followed, it usually takes over a year gluten-free for that to occur.

“To make things even harder for patients to maintain a strict diet, gluten-free products are not exactly tasty,” Dr Tye-Din says.

The temptation is to throw caution to the wind and put up with feeling unwell, however it’s the long-term damage and risk of potentially life-threatening complications that is the real concern.

“Understanding the basis for coeliac disease was the key for designing a new treatment that could potentially replace the need for a gluten-free diet”, Dr Tye-Din explains.

For the past decade Dr Tye-Din has worked alongside Dr Bob Anderson, based in Boston with ImmusanT Inc., the company leading the development of NexVax2. Dr Anderson’s work set the scene for understanding the toxic protein fragments (or peptides) of gluten by studying patients with coeliac disease after they took part in a 3-day ‘gluten challenge’.

Utilising this approach, Dr Tye-Din and his team produced a comprehensive ‘road map’ of the toxic gluten peptides in wheat, rye, barley and oats; the culprits in coeliac disease. With the aid of a powerful computer algorithm they were able to design and manufacture a collection of more than 18,000 gluten peptides spanning all these cereals.

Dr Tye-Din then used the peptides to set up a three-day gluten challenge with more than 300 volunteers from the Coeliac Society.

Remarkably, the research team found that just three gluten peptides account for most of the immune reaction coeliacs experience after consuming wheat, rye, barley or oats. It is these three peptides that form the basis for NexVax2 and allow new applications such as improved diagnostic tests for coeliac disease to be developed.

“The other significant finding of our work is that particular genes associated with coeliac disease influence the ‘flavour’ of the immune response. We know that almost every coeliac patient has the genes HLA DQ2 and/or HLA DQ8. Which particular gene(s) a person with coeliac disease has will determine which gluten peptides are toxic to them.

“We’re entering an era when knowing the genetic profile of a person will have a direct impact on treatment. A successful immune therapy will dramatically change the management of coeliac disease, and potentially provide a new approach in the treatment of a variety of other debilitating human immune diseases.”

On April 26, a free public evening lecture will be held at the University of Melbourne as part of International Day of Immunology celebrations. Hear more on the link between genes and the immune response as well as the latest research into transplantation and therapies for HIV/AIDS.

For more information and to register,
www.dayofimmunology.org.au