12/28/2010 --- A breakthrough drug containing theobromine, an ingredient naturally present in cocoa and chocolate, is entering the final stages of human clinical trials for the treatment of persistent cough, researchers announced. The drug is being jointly developed by SEEK, a leading UK privately-owned drug-discovery group, and could be on the market within two years.

A persistent problem

Persistent cough is a very common condition, afflicting over 800 million worldwide, with an estimated 12% of the general population (7.5 million in the UK), having the symptom on a daily or weekly basis. Persistent cough, defined as a cough that persists for more than two weeks, has numerous causes but falls into two broad categories; that causing an asthma-like syndrome of the airways and oesophageal reflux. Failure to treat cough can lead to enormous consequences in terms of loss of employment, healthcare utilisation and a psychosocial morbidity.

The issue with current opioid treatments

The majority of currently-available cough products soothe the symptoms rather than deal with the root cause of the problem. Those that do more than soothe are all codeine-based - an opioid - and have recently been shown to have serious safety concerns due to differences in the way codeine is metabolised into morphine. So much so that, in October 2010, the MHRA (Medicines and Health products Regulatory Agency) advised that codeine-containing over-the-counter liquid medicines should not be used for cough-suppression in children and people younger than 18 years, as "...overall, the risks of over-the-counter cough medicines for children containing codeine outweigh the possible benefits".

No new non-opioid based treatment has been developed in two decades, and Professor Alyn Morice, a leading expert in the treatment of cough, and Head of the Hull Cough Clinic, highlights the problem: "Thousands of people across the UK suffer from persistent cough, and due to the drawbacks of current opioid drugs such as codeine, we are in desperate need of a non-opioid treatment with a drastically improved side effect profile for patients."

Human trial research in Korea has shown that theobromine has none of the side effects associated with standard drug treatments for persistent cough.

The benefits of theobromine

Theobromine has been shown to inhibit the inappropriate firing of the vagus nerve, which is a key feature of persistent cough. This peripheral mechanism of action differentiates theobromine from codeine and other centrally acting agents, and lessens its lower central nervous system side effects.

Other beneficial effects of theobromine are a well-known; in modern medicine, it has been used as a vasodilator (a blood vessel widener), a diuretic (urination aid), and heart stimulant. It is found in significant quantities in cocoa-based products, including chocolate, and is a metabolite of caffeine.

Availability within two years

Following consultation with a European Medicines Agency (EMA), the single Phase III trial of theobromine (BC1036) is expected to begin in the UK in the first half of 2011. The drug has the potential to be on the market in Europe within two years from trial commencement, subject to receiving final marketing authorisation.

Manfred Scheske, CEO of Consumer Health at SEEK said: "Persistent cough is a very common condition, often lasting for weeks after a viral infection. It can be difficult to treat, especially since it is not possible to give large doses of opiate-based medication to patients due to side-effect issues. I am very excited to announce the progression for the late-stage development of BC1036, which has the potential to dramatically impact the treatment of persistent cough and could greatly benefit the quality of life of persistent cough sufferers."