Scientists at St George’s, University of London and the University of Manchester have received an additional Seeding Drug Discovery award of £390,000 from the Wellcome Trust to explore a new class of experimental drugs that block the trigger of allergic reactions before symptoms show.

The team is developing a series of drugs based on novel chemical compounds known as Allergen Delivery Inhibitors (ADIs). Unlike existing medicines, these compounds target the substances that can trigger allergies and asthma attacks directly. This means that they have the potential to provide relief to people already suffering with allergies, as well as reducing the risk of minor allergies escalating into more serious conditions.

 



In 2009, the researchers were awarded a £4.3 million Seeding Drug Discovery award to investigate ADIs as a potential treatment for asthma and allergy. In the course of that project, they have identified a novel chemical series that shows promise as a preventative treatment. The new funding will be used to explore this further with a view to identifying a lead compound that could be developed into a drug.

Asthma and allergic conditions such as rhinitis, conjunctivitis and dermatitis are escalating problems expected to affect more than 100 million people globally by 2011. In the UK, 5.2 million adults and 1.1 million children currently receive treatment for asthma, creating a significant social and healthcare burden for the NHS.

The first ADI drug being developed by the team – in collaboration with the expert medicinal chemistry partner Domainex – targets house dust mites, globally one of the commonest causes of domestic allergy and a key trigger of asthma attacks.
Dust mites excrete particles, amongst which are powerful enzymes that, when inhaled, can cause an inappropriate immune reaction in people who are prone to allergy, causing damage to the lining of the airways. These allergenic enzymes are abundant in the environment, so they cannot be avoided and susceptible people are constantly at risk.

The team has developed ADIs that bind to the dust mite particles and block their enzymatic activity. Experimentally, these inhibitors reduce the intensity of reactions in established allergy and can even prevent allergy from occurring.

“A compelling feature of the ADI approach is its attack on the pinnacle of the cascade of events that leads to an allergic reaction,” explains lead researcher Professor Clive Robinson from St George’s, University of London. “Existing medicines target the allergy cascade at a lower, more complex level where success in the discovery of new drugs that modify allergic diseases is notoriously hard to achieve. At present, patients have to rely on therapeutic approaches which have seen no fundamental advances in the past 20 years.

“Used alone or in combination with existing treatments, our investigations indicate that they should improve the quality of life for many patients with allergic disease and may enable some to manage without any other form of treatment,” continues Professor Robinson. “Additionally, ADIs may provide relief for some patients who do not respond well to existing medicines.”

“We have made outstanding progress in refining these molecules into a drug that will be safe and effective in humans. However, much work remains before a medicine will be available,” concludes Professor Robinson.

Dr Rick Davis, Business Development Manager at the Wellcome Trust, commented on the award: “Allergy is a source of misery for millions worldwide and represents an area of huge unmet medical need. The St George’s-Manchester collaboration has made excellent progress in this area and we are pleased to provide continued support for this project.”

Once a lead compound has been identified, the next phase of work will be to refine the drug candidate to take forward into human clinical trials to assess its safety, tolerability and efficacy.