World first: Celiac disease VACCINE trialed in Australia – April 09. Will it cure all celiacs & will you still need or want to eat Gluten Free Food?

If you are a celiac, your miracle cure is under way - being trialed in Melbourne Australia from April 2009! It could conceivably desensitize people with celiac disease to the point that the villi in their small intestine are not damaged by the gluten protein. However with the need for extensive testing in this three phase trial, the vaccine may not be ready for release for several years.

Before we go into the details of such a cure it should be noted that this vaccine might not be a ‘magic bullet' that makes people permanently immune to the gluten protein, it might 'only' desensitize them. Also be aware that if you choose to undertake the ‘therapy' there are no guarantees of how you will react, and the only way to regularly check to see if you have been ‘cured' would be regular intestine biopsies. As it is known that some people take over two years to heal their intestines from gluten damage, how risky will this strategy be? It is expected that testing will be extensive so these questions may all sit under the ‘devil's advocate' category, and all may be well.

An even more philosophical question is what effect covering up the cause of your disease will have on your body. Books have been written that suggest that it is the increased gluten potency in wheat and other gluten grains as well as increased use in manufactured foods that has led to an overdose of gluten. Our bodies then pass a ‘tipping point' where our genetic predisposition to CD turns into an active disease. If this is true, how wise would it be to continue ingesting unnaturally high levels of gluten, once ‘cured' just because we can? Sure it would make life simpler not following a gluten free diet, however maybe we should wait for gluten to be decreased at the source, the growing fields, before we return to a gluten filled diet.

Different types of celiac disease identified

With all these issues under consideration, I am sure that every celiac would still be interested in a ‘cure'. A July 2007 article based on research conducted in Victoria, Australia, showed that "Celiac disease - is strongly associated with human leukocyte antigen (HLA) DQ2 and to a lesser extent with HLA DQ8."

"HLA genes are part of the major histocompatibility complex (MHC), which plays a pivotal role in the immune system. HLA-DQ2 mediated celiac disease is common in people of European ancestry, with about 90 per cent of sufferers positive for DQ2. Another five per cent possess HLA DQ8. In China and East Asia, DQ2 genes are rare while DQ8 genes are as common as in Europe."

So it appears that this preliminary research has been able to isolate two main versions of celiac disease. However the molecular workings of the immune response in the two antigens appear to be very different. The researchers discovered that T-cells in people with DQ8-associated celiac disease reacted quite differently to the small proteins in gluten than the T-cells in people with the DQ2 form of the disease.

"At the moment a gluten-free diet is the only treatment for celiac disease but nearly half the people on the diet still have damage to their small intestine. Consequently other therapies, including a vaccine and three different drugs, are in various stages of development. The research team believes celiac disease might be the first example of an immune disease where treatments are customized according to the genetic make-up of the patient."

The celiac vaccine discovery

The discovery that lead to the creation of the vaccine was that the one critical part of wheat gluten protein that was toxic was the common genetic version (HLA DQ2) of celiac disease. "As much as the identity of the toxic component of gluten was important, it was the way in which it was found that has proven to be even more important. By eating gluten in wheat, rye, or barley for three days (even a single meal will suffice in some people), immune cells (T cells) that damage the small intestine are mobilized into blood for a few short days. The T cells in blood can be monitored and analyzed to define what part of gluten they recognize. The parts of gluten recognized by the vast majority of T cells involved in celiac disease can be condensed to a few "short" fragments of gluten that remain after its digestion in the gut. These gluten fragments can be synthesized using fairly standard chemistry and are the basis for the celiac vaccine."

The Celiac Vaccine Trials

The original research began at Oxford England in 1997. The work continued in Australia in 2002 and by April 2009 Bob Anderson from the Walter and Eliza Hall Institute of Medical research (Melbourne, Australia) will commence the first world trials of a celiac vaccine that could reduce or eradicate the need for being gluten free. In fact Bob Anderson calls the vaccine a "next-generation desensitization therapy" that has been successful in mice and is soon to be tested on celiacs.

"The vaccine will be tested on 40 volunteers with celiac disease over 11 months to establish that it does not harm them. In a subsequent phase 2 trial, which is designed to find out if the treatment is effective, volunteers will receive the treatment and then be challenged with foods containing gluten. Their immune response and intestines will then be examined to see if a tolerance to gluten has developed. The therapy involves repeatedly injecting solutions of gluten at increasing concentrations. The aim is to desensitize the subjects slowly, in a similar way to hay fever and dust allergy desensitization treatments."

Testing process

"For a new drug to be accepted for use in people in Australia, Europe, or North America it must have progressed successfully from Phase 1 (safety) studies usually involving up to about 30 volunteers, to Phase 2 (efficacy) studies to show that "it works" in people with the medical condition of interest (typically about 200 volunteers in several locations around the world), and to Phase 3 (similar to Phase 2 but involving several thousand volunteers in many sites around the world)."

The celiac vaccine future

Due to difficulties in funding, Bob Anderson (Walter and Eliza Hall Institute) co-founded a commercial company called Nexpep to develop the vaccine. Nucleus Network, Centre for Clinical Studies (CCS) in the Alfred Hospital in Melbourne, will be conducting the Phase 1 clinical trial.

The difficulty he has faced, besides the technical issues, is the low diagnosis level of celiac disease and the mass of associated symptoms has made a vaccine cure unattractive to traditional pharmaceutical companies. These companies always prefer well defined markets to accurately forecast payback periods for their R&D and marketing expenses.

The facts are that for this vaccine to prove financially viable, The US will need to approve the drug and doctors and celiacs will need to accept the treatment. One report estimates that only 600,000 people are diagnosed with celiac disease (out of the 5 million with celiac disease in North America and Europe).  

Compounded to the funding challenges is that previously, globally, there have only been three "randomized, controlled" studies of the gluten free diet - one in children and two in adults - the largest with 57 participants."

The assessment of the vaccine treatment will require repeated endoscopy and collection of small intestine biopsies which are expensive and un-enjoyable for volunteers. However a recent trial in Italy has shown that biopsies are still the only ‘almost' guaranteed method of assessing gluten damage. The study findings showed that "two years after adopting a gluten free diet, about half those people diagnosed with celiac disease continued to have villous atrophy as severe as when they were first diagnosed. Only about one in five of those with severe intestinal damage (villous atrophy) on a gluten free diet had raised (abnormal) blood levels of transglutaminase antibody, meaning that standard blood tests to monitor disease activity were relatively ineffective."

So while the development of this vaccine is an important step in potentially eradicating celiac disease, philosophical questions still remain as issues for the long term efficacy of the vaccines. As an Australian first, this research is applauded by the gluten free community. We wish the researchers and medical staff all of the best in demystifying this illusive disease.

Article references are available on the gluten free pages website.