New discovery may lead to new medications....
Public release date: 20-Oct-2004
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Contact: Sarah L. White, Ph.D.
Ludwig Institute for Cancer Research
p110 delta: A key player in the allergic response
Potential new target for drug development
(London - October 21) -- The suffering of millions of people with allergies could one day be eased thanks to new research from UK investigators. Findings from the University College London Branch of the Ludwig Institute for Cancer Research (LICR), published in this week's Nature, detail how inactivating a key signalling molecule called p110delta reduced the effect of allergies on mice.
Allergies are essentially inappropriate responses by the immune system to allergens such as pollen, dust, insects and animals. This results in the activation of immune cells, called mast cells, which release inflammatory agents, leading to the symptoms so many of us know so well: runny noses, itching eyes, coughing, skin rashes and wheezing.
Dr. Bart Vanhaesebroeck and his team at LICR, together with collaborators from Novartis Respiratory Disease Centre headed by Dr Peter Finan, found that inactivating p110delta in mast cells substantially reduces the allergic response seen in mice. In mice lacking the gene for p110delta, the allergic response was reduced substantially; in normal mice that had been treated with an experimental drug inhibiting p110delta, the allergic response was stopped completely.
Allergies have increased dramatically over the past 20 years, and new treatments are clearly needed. Experts estimate that, in the UK alone, 1 in 3 people will suffer from some form of allergy during their lifetime; some 9 million people suffer from hay fever, 6 million from eczema and 5 million from asthma each year. In the most extreme circumstances, an allergic reaction can be life-threatening or even fatal. This is commonly seen in peanut and drug allergies.
According to Mr. Khaled Ali, the lead author of the study, current therapies to treat allergies are mainly non-specific, targeting the symptoms of allergy rather than targeting what is actually happening in the mast cells themselves. "It is hoped that by targeting p110delta, we can directly stop mast cell activation and, in doing so, help end the misery they bring to many sufferers."
"We have to remember though that mice are not the same as humans," cautions Dr Vanhaesebroeck. "Our work points towards a promising future for developing inhibitors for allergic conditions, but we are still a long way from developing a drug for human patients." The LICR group's research efforts are also focused on their findings that p110delta could also play a role in certain tumours, like leukemia, and that targeting the p110delta pathway may one day also be useful in the treatment of cancer.
This study was conducted by researchers from the University College Branch of the Ludwig Institute for Cancer Research, London, the Novartis Respiratory Research Centre Horsham, Frimorfo Ltd, the Department of Biochemistry of the University of Dundee, the Department of Biochemistry and Molecular Biology of University College London, and the Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health.