COMMERCIAL PROFILE; SCIENCE FOUNDATION IRELAND:Prof Luke O'Neill, who scooped Science Foundation Ireland's Researcher of the Year award, is behind drug development firm Opsona which will begin clinical trials on a new treatment for rheumatoid arthritis

THE NEXT blockbuster drug for the treatment of rheumatoid arthritis could be developed as a result of the work of Science Foundation Ireland's Researcher of the Year, Prof Luke O'Neill of the school of biochemistry and immunology at Trinity College Dublin. O'Neill's research field is in the area of immunology and has already resulted in the establishment of drug development company Opsona Therapeutics. The company will begin clinical trials next year on a new product for the treatment of rheumatoid arthritis and other auto-immune conditions.

O'Neill also won the 2009 RDS Irish TimesBoyle Medal for Scientific Excellence for his research, which focuses on "toll-like receptors", a family of proteins that respond to infection by triggering inflammation in order to eliminate invading microbes. His research concentrates on the molecular and cellular basis of inflammation and examines new treatments for diseases involving the immune system. He also studies innate immunity, the part of our immune system that does not make use of antibodies but fights infection in a non-specific way.

"I'm very honoured to have won the two awards," he says. "I was runner-up for the Boyle Medal twice so it's nice to actually win it. This is the first year of the Science Foundation Award so it's a great honour to be the first winner. It's also very good to see another award for science in Ireland - there aren't enough of them. Apart from the Boyle Medal I think the RIA is the only other body which has an award for scientific research in Ireland."

He is especially pleased with the Science Foundation Ireland (SFI) award given his long association with the organisation. "SFI has what are called Principal Investigator awards to support research and I am lucky enough to be on my second programme of funding under this," he notes. "I got my first funding award in 2002. It's a five-year programme and is really very good. In the current round we have €3.5 million over five years and this allows you to build up a strong team of good researchers. You get a good slug of money in advance to do this. It would be impossible otherwise."

This type of support is essential for research in Ireland, he believes. "SFI has been a godsend," he says. "The US has various funding programmes like SFI and in the UK they have the Wellcome Trust which funds scientific research. What SFI is doing is bringing us up to standard international practice."

The Principal Investigator programme is not the only SFI support he receives as he is also involved in the Immunology Research Centre (IRC), an integrated collaborative effort bringing together the leaders in the field of immunology in Ireland, with industrial partners such as Merck/Schering-Plough to understand and exploit the interface between innate and adaptive immunity. The five-year research programme is funded by a Strategic Research Cluster award from SFI and is led by Trinity College Dublin in collaboration with NUI Maynooth.

Given this high level of support he is naturally concerned about possible Government cutbacks in this area. "My biggest fear is that the Government will reallocate the money into other things," he says. "As an Irish scientist I am very proud of SFI. They have some fantastic people in there and they have a very rigorous peer review process which is well up to international standards. There are lots of good metrics out there to show that SFI is a very good programme."

And it is the international dimension which is most important. "Scientific research is an international game. You can only be a player if you're recognised internationally," he argues. "SFI does punch above its weight internationally and that's very important. Although I'm very pleased to have won these awards, saying that you're the best researcher in Ireland is a bit like saying you're the best in Wicklow or whatever; it's the international scene that counts."

O'Neill certainly possesses those international credentials having gained his PhD in Pharmacology at the University of London (Royal College of Surgeons) in 1988 before moving onto post-doctoral research at University of Cambridge prior to his return to the biochemistry department in Trinity.

"All my career has been about inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, asthma and Crohn's disease," he explains. "The work that we do is to try to dig down to find out what's going on to cause these diseases. We look at the different component parts. It's a bit like a car mechanic lifting the bonnet to see what's going wrong. When we find the bit that's broken we then try to see if we can fix it."

This brings us to the toll-like receptors (TLR) that he specialises in. "Proteins get over-produced in certain situations. It's a bit like friendly fire or civil war in military terms. The body's immune response goes out of control and this is what causes the swelling in joints which is typical of rheumatoid arthritis."

There are already drugs like Wyeth's Enbrel, which is manufactured in Grange Castle in west Dublin, which treats conditions such as rheumatoid arthritis. "I was involved in the development of Enbrel," O'Neill adds. "It is a hugely successful drug which will have €7.4 billion in sales this year. But what it does is mop up the excess proteins. What we are trying to do with our research is turn off the tap at source."

This research has been enabled by the discovery of TLRs in the late 1990s. "These are the switches which turn on the tap if you like," he explains. "This gave us a new target to aim at when developing treatments. We are getting very close to the source now. But we still don't know who actually turns the tap on. We know that infection causes it in certain circumstances but sometimes there is no infection or none that we can find anyway. We still don't know who God is in this one."

This is part of the reason why research like O'Neill's is so important. "One hundred years ago we didn't know what caused TB let alone being able to cure it. We've come a long way but we still only know about 10 per cent of what's going on. We've got a long way to go. In fact, it's a wonder that drugs work at all given the extent of our ignorance."

Notwithstanding this, the company he helped found, Opsona Therapeutics, could be on the cusp of a major breakthrough. From a financial point of view it is certainly very healthy having raised funding of €18 million earlier this year from a consortium of investors which included Novartis Venture Fund, Fountain Healthcare Partners, Inventages Venture Capital and Seroba Kernel Life Sciences.

"There are 10 types of toll-like receptor," O'Neill explains. "And we are specialising in one of them - TLR2, and working on an antibody to it."

TLR2 is very important not only because of its role in rheumatoid arthritis but also because it has been found to be responsible for certain inflammatory kidney diseases as well as for problems following heart attacks. The potential heart treatment is very interesting.

"After a myocardial infarction or heart attack the damage done to the heart tissue is actually as a result of the reprofusion of blood into the heart after the doctor releases the flow by removing the clot. If you were to give our drug during the reprofusion it will help reduce the inflammation and therefore limit the damage done. If our trials on the drug next year are successful we will move onto a phase two trial. The drug certainly could be a new blockbuster like Enbrel. After that the natural route would probably be to sell the company to one of the major pharmaceutical firms and use the money for other research."

He believes that none of this could have been achieved without SFI. "We couldn't have got the international credibility required to raise the funding without the SFI support in the work leading up to the founding of the company. The whole idea of funding basic research is not just to make new discoveries, it's to give our researchers the international credibility they need to get commercial funding later on."