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Novel preventative and therapeutic treatments for coeliac disease

Alex Gazzola reports on a talk by Dr Julio Bai of Hospital de Gastroenterología, Buenos Aires, at the Gastro2009 conference on new approaches to tackling coeliac disease, who believes alternatives to a GF diet are needed because the diet is expensive, difficult - and compliance is sometimes poor.

Dr Bai’s encouraging talk began by clarifying why new approaches were needed in tackling the problem of coeliac disease (CD).

In his home country of Argentina, he explained, 35% of the energy in the diet is supplied by wheat, and the grain is particularly difficult to avoid. A gluten-free (GF) diet has implications on nutritional intake, is costly, and traces of gluten are found even in supposedly GF cereals, due to contamination. More worrying is the issue of non-compliance: in Argentina, 50% of diagnosed coeliacs do not adhere strictly to GF, and the potential future clinical implications that brings are a clear concern.

With regards to primary prevention, we know that breastfeeding is important in reducing the risk of developing CD, while artificial feeding is associated with an increased risk, and with more advanced gastrointestinal lesions.

There is one ongoing prospective trial on the effect of delaying the introduction of gluten in babies with a high risk of developing CD (ie with a parent or sibling with CD). Taking place in Italy, and co-ordinated by Carlo Catassi, over 700 babies have been recruited and have been randomly divided into two groups – one of whom receiving gluten for the first time at six months, the other of whom at twelve months. Five years on, results show that 8% of babies in the six-month group have developed gluten sensitivity, while only 2% of babies in the twelve-month group have. While a remarkable result, Bai cautioned that this may not indicate a different eventual prevalence, and that delayed introduction of gluten may only cause delayed initiation of CD, so further follow-up over coming years will be needed.

Bai also remarked on the exciting PREVENTCD Europe-wide project, which started in 2007, and is based on the hypothesis that it is possible to induce tolerance to gluten in at-risk infants by introducing to their immune systems small quantities of gluten during breastfeeding. Previous studies have indicated that there may be an ideal ‘window of opportunity’ of age four-to-six months for introduction, and the study is exploring this using a randomised double-blinded study, with one group of breastfed babies receiving a daily pill of 100mg of gliadin (the toxic constituent of wheat gluten) and the other receiving a placebo. It is hoped the eventual results will help shape future weaning advice for high-risk babies in Europe.

And then there are the pharmacological interventions for existing CD. Bai suggested there are four possible goals for future treatments:

1. Treatments which are adjuvants to GF.
2. Treatments which help minimise the effects of hidden gluten in the GF diet.
3. Treatments which allow moderate gluten consumption.
4. Treatments which replace GF and allow full gluten consumption.

There are five treatments presently at different trial stages.

1. The NexPep vaccine – a peptide-based therapeutic vaccine with the potential to treat 80% of those with CD. Phase 1 trials are just beginning in Australia.

2. Hookworm / helminthic therapy – inoculating CD patients with a harmless hookworm to explore whether it can interfere with the immune response and alter the responsivity to gluten. Phase 2 trials are starting now.

3. ALV003 – an enzyme therapy which helps break down the toxic fragments of gluten when taken before a gluten-containing meal. Presently in phase 2 trials.

4. CCX-282-B – an anti-inflammatory drug which works by reducing the movement of certain immune cells from the bloodstream into the gut wall. Presently in phase 2 trials in Finland.

5. AT-1001 – a drug which reduces the gut’s permeability to gluten, now in phase 3 trails in North America, and showing a lot of promise.

It will probably be another ten years before some of these potential treatments are widely available commercially, cautioned Bai, but there is clearly cause for some optimism.


Click here for more articles on the management of coeliac disease

 

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