A Southampton-led clinical trial could pave the way to a new treatment for virus-induced asthma attacks. New Boundaries speaks to Professor Stephen Holgate about this latest trial and the University’s world-leading asthma research.
Asthma is one of the most common chronic conditions in the developed world, affecting one in 11 children – and it is on the increase. Winter months can be a particularly worrying time for asthma sufferers because cold and flu viruses trigger more frequent asthma attacks; this could all change thanks to a phase II clinical trial, led by Southampton researchers in partnership with the spin-out company Synairgen.
By studying the cells from the lining of the lungs, Southampton researchers discovered several years ago that people with asthma are unable to fight off colds and flu as effectively as people with healthy lungs. Professor Stephen Holgate, a world-class researcher and leader in the medical community who has been researching asthma at Southampton for the past 35 years, explains: “Our most exciting discovery so far has been that asthmatics don’t make enough of a type of protein – interferon beta – in their airways, which would normally defend them against viral infections such as the common cold. This led to our establishing a University spin-out company, Synairgen, in 2004 to develop a treatment to make up the deficiency.”
The researchers are now trialling an aerosol spray of interferon beta to boost the immune system of people with asthma. Due to be completed at the end of this year, the phase II clinical trial includes volunteers with asthma who will be dosed with interferon beta when they catch a cold or flu. If the treatment proves effective, it could significantly improve the quality of life for people with severe asthma and reduce the number of patients admitted to hospital with asthma attacks in the winter months.
A translational approach
Over the past 30 years, Southampton researchers have been translating fundamental science to clinical practice to improve the lives of people with asthma. The interferon beta clinical trial is just one example of this. Stephen explains: “Doing medical research to benefit patients directly has been at the core of our philosophy since this medical school was founded.” With strong links between the medical school and the hospital trust, Southampton remains uniquely poised to move discovery science into clinical trials, leading to a smooth transition of research in the laboratory to its application in the clinic.
The award of special facilities to Southampton has been a great help in pioneering respiratory research, explains Stephen: “Our Wellcome Trust clinical research facility was one of five awarded to medical schools around 10 years ago and more recently the University was one of three centres in Britain to be awarded a Biomedical Research Unit for respiratory and nutrition research.” With the consent of volunteer patients, these facilities give researchers access to tissue samples from routine procedures for the study of diseased cells, enabling them to find out what has gone wrong in conditions such as asthma.
Having consent to use tissue samples for research has enabled Stephen and his colleagues to make fundamental discoveries about asthma. “The interferon beta discovery emerged precisely because we are able to study disease in human tissue rather than in animal models,” explains Stephen. More recently, Stephen’s team has now shown that interferon beta can also protect against influenza viruses, particularly avian flu and swine flu – and through the Biomedical Research Unit they will soon be running a further clinical trial to investigate how effective the treatment is for groups – such as diabetics, asthmatics, pregnant women and children – who are most at risk if they develop influenza. Stephen himself has played a key role in the University’s translational research. Since the late 1970s, he has been striving to find the cause of allergic asthma – the most common form of the condition. This year he was awarded a CBE in the New Years Honours for his services to clinical science.
Building on success
Respiratory research at Southampton has had many successes over the years. For example, in 2000, Stephen’s team identified the first novel asthma gene – ADAM33 – which they reported in the journal Nature in 2001. Over the past 10 years the team has studied the gene in detail, improving the knowledge base on how it can cause asthma to develop in young children. “We have shown that this gene can become abnormal at very early stages of life – even in developing babies in the womb. It’s one of a series of genes the environment modifies in early life to make asthma more likely to develop in children. The gene is also involved in making the disease more chronic and severe,” says Stephen. Researchers are now building on this work to discover what makes asthma a chronic condition that persists throughout life; they are making exciting links between respiratory research and developmental science, with new studies looking at ways to prevent children developing asthma by controlling diet in pregnancy and early childhood. “This links to an area of science that the research community is very excited about: epigenetics – the study of how the genes are switched on by the environment. We’re looking at what it is in early life that switches on these genes and makes children asthmatic,” says Stephen.
Exchanging ideas with the research community around the world has been key to the success of Southampton’s respiratory research. “Southampton is among the top five in the world in asthma research; one of the most powerful things to enable this is the fact that over the last 20 years a lot of very talented people from across the world have come to do their training at Southampton, bringing with them originality and fresh ideas,” explains Stephen. “Several of our researchers have also won awards to spend two or three years in the best laboratories in the world. When they come back to Southampton they bring new techniques to apply to human-based discovery science, which is a tremendously successful model,” he adds.
Multidisciplinary research and partnerships with industry and charities also play a key part. Many Southampton PhD students are funded jointly with charities, industry and other academic units at the University of Southampton, such as Biological Sciences, Chemistry and Engineering Science. This is leading to fresh ideas and the development of new diagnostic tests by bringing expertise together across the disciplines. Respiratory research at Southampton is certainly in good health. “I am still at Southampton after 35 years for a very good reason: this university has a huge amount to offer. You can do as much and more here to develop your research career as any other institute in the world.”
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