Fresh funding gives hope to new generation of asthma and allergy drugs

(PhysOrg.com) -- Scientists at The University of Manchester and St George’s, University of London, 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 arise.

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 £4.3million 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 100million people globally by 2011. In the UK, 5.2million adults and 1.1million 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.

“Millions of people worldwide are allergic to the tiny house dust mites that live in our homes, cars and other building that we frequent,” said Professor David Garrod, in Manchester’s Faculty of Life Sciences. “ADIs attack the root cause of the allergy by preventing the inhaled mite enzymes from starting the allergic response. Currently available treatments alleviate symptoms but do not prevent them from occurring. This new grant from the Wellcome Trust will increase our potential to develop ADIs, which will provide a new dimension in the treatment and prevention of allergy.”

Lead researcher Professor Clive Robinson from St George’s, University of London, added: “A compelling feature of the ADI approach is its attack on the pinnacle of the cascade of events that leads to an allergic reaction. 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. Additionally, ADIs may provide relief for some patients who do not respond well to existing medicines.”

Dr Rick Davis, Business Development Manager at the Wellcome Trust, said: “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.

Provided by University of Manchester