Study may lead to new drugs to treat cough

Jul 9 2009

Scientists investigating the cough reflex have discovered a new group of molecules on the surface of nerve cells that make us cough when irritated.

The findings, to be presented at the British Pharmacological Society's Summer Meeting in Edinburgh this week, could lead to new drugs to treat cough, which when chronic affects about 10% of the UK population.

"Cough is the commonest symptom for which medical advice is sought and accounts for over half of new patient consultations to a GP," said Professor Alyn Morice, a Clinical Pharmacologist at the University of Hull, who is leading the research.

"Chronic cough can be socially isolating and disabling and people come from all over Europe to my cough clinic because the cough is ruining their lives, yet current treatment options are limited with remedies little better than honey and lemon."

Professor Morice and his team at Castle Hill Hospital in Hull have identified a group of protein molecules called receptors that sit on the surface of nerve cells and allow signals to be passed inside nerve cells.

The team have shown that the 'very cold' receptor (TRPA1) on nerve cells is stimulated by a cinnamon extract in normal volunteers, leading them to cough. Furthermore, the researchers have successfully cloned the TRPA1 receptor to allow them to investigate the pharmacology of these nerve endings.

"The receptor which has had the most drug development focused on it is the hot receptor TRPV1 , which is stimulated by capsaicin, the extract of chilli peppers, where a number of companies have produced potential drugs to block the receptor and have taken them as far as the clinic," said Professor Morice.

"Unfortunately, in this particular receptor's case it seems that blocking the receptor led to patients developing a higher body temperature and they were also less capable of feeling heat, which of course could be dangerous, so much of the development has stopped.

"The TRPA1 receptor that we have identified as a cough receptor and recently cloned is more interesting because it is set off by a much wider range of substances. However, once the results are published it will probably take up to five years for drug companies to develop blockers as far as the clinic."

Professor Morice's team have just begun a large-scale patient study that will try to identify existing blocking agents for this new family of receptors, although the ultimate goal of research into cough is to restore the cough reflex to normal levels, rather than stop it altogether.

"When people have a cough they have a heightened sensitivity, which we can demonstrate in the laboratory," added Professor Morice. "However, we don't want to eliminate cough in patients because it is vital to keeping people well - it stops us getting pneumonia - so a return to normal sensitivity is the goal.

"We already have some agents that we can use but the effective ones, such as morphine, have side-effects, so our aim is to find an agent that works that has a good side-effect profile."

http://www.bps.ac.uk/