Exeter researchers awarded nearly £1 million to investigate COPD

Exeter researchers awarded nearly £1 million to target lethal lung disease

Exeter researchers have been awarded a grant of almost £1 million to develop new compounds which could treat the UK’s second most common lung disease.

Professor Matt Whiteman, Dr Chris Scotton and Dr Mark Wood, of the University of Exeter, were awarded the grant by the Medical Research Council (MRC) to investigate the use of newly designed compounds in the treatment of chronic obstructive pulmonary disease (COPD).

The term COPD describes a group of lifelong, progressive lung diseases including emphysema, which affects the small air sacs in the lungs, and chronic bronchitis, affecting the airways. According to the World Health Organisation, the disease is the world’s third biggest killer and is responsible for more than 3 million deaths worldwide each year. The number of people living with COPD continues to rise, and there are currently no treatments which halt progression of COPD.

However, compounds invented and patented at the University show promise in treating the disease.

First developed by Professor Whiteman and Dr Wood in 2012, the patented compounds deliver small doses of hydrogen sulfide (H₂S), a gaseous molecule which naturally occurs in our bodies, to cells.

Hydrogen sulfide can act on mitochondria, which are the specific cell components that control energy production and help regulate the body’s response to inflammation. Excessive inflammation can result in cells becoming stressed. Research has shown that under these circumstances, cells can use hydrogen sulfide as an “emergency energy source”.

The potential drugs, collectively known as mitochondrial-targeted hydrogen sulfide donors (or “mtH₂SD” for short), could have numerous uses in healthcare. The first mtH₂SD drugs developed were also effective at reversing brain injury after cardiac arrest, a project named in the Times Higher Education’s “20 ideas from UK University’s that will change the world”.

More recently, mtH₂SD compounds were involved in a breakthrough in reversing key aspects of human cell ageing, as well as reversing injury after blunt chest trauma and shock. The research team are now exploring their potential in repairing lung damage caused by COPD.

COPD is characterised by chronic inflammation in the lungs, and damage to the cells that are vital for controlling this inflammation and initiating repair - causing hydrogen sulfide levels to drop.

In early studies in mice using the first mtH₂SD developed (AP39 and Rt01),  these compounds  rescued the lung from damage by controlling inflammation, improving lung function and preventing the irreversible damage to the tiny air sacs (alveoli) in the lung. In the new grant, the researchers will test improved versions of these molecules in a unique animal model developed at the University of Newcastle, Australia.

Dr Scotton, of the University of Exeter Medical School, and Chairperson of the British Association for Lung Research, said: “Chronic obstructive pulmonary disease is a global problem. In the UK alone, over a million people suffer from this disease – and the direct cost to the NHS is nearly £2 billion a year! We desperately need to find better treatments to offer to patients, and we hope data from our project will significantly advance the search for new and effective therapies.”

Professor Whiteman, of the University of Exeter Medical School, said: “With the help of the Medical Research Council, we now have another dedicated medicinal chemist and several research staff to evaluate a series of novel potential drugs we have designed, to treat this awful debilitating disease and really push this research forwards towards testing in the clinic.”

In another project, a clinical grant recently awarded by the Physicians’ Services Incorporated [PSI] Foundation, Canada, the team will be looking into the use of AP39 for reconditioning discarded human kidneys to make them fit for transplant. That project will be a partnership with the Matthew Mailing Center for Translational Transplant Studies, University of Western Ontario, Canada, and will build on promising previous research on the subject.

Date: 4 September 2018