Two of Britain’s leading biomedical researchers, Professor Sir Ravinder Maini and Professor Sir Marc Feldmann, have today been awarded the 2014 Canada Gairdner International Award for their research into anti-TNF (tumour necrosis factor) treatment, which, in significant part, was funded by Arthritis Research UK. The Canada Gairdner Award, recognised internationally as one of the top prizes for biomedical research, highlights and celebrates those scientists who have made groundbreaking medical discoveries that have had a profound effect on the understanding and awareness of human biology and disease. The pioneering research studies celebrated by the awards often lead to the diagnosis, treatment and cure of diseases.
In the mid-1980s Professor Sir Ravinder Maini and Professor Sir Marc Feldmann, then based at Arthritis Research UK’s Kennedy Institute of Rheumatology in west London, discovered which molecules in rheumatoid arthritis were driving the inflammation and destruction of joints, enabling them to develop a viable and effective treatment for rheumatoid arthritis. The research has had a major impact worldwide, providing new and effective treatment for resistant rheumatoid arthritis patients, which has benefitted millions of patients with severe disease.
Rheumatoid arthritis is a chronic inflammatory disease affecting the immune system. It affects around 400,000 people in the UK, and causes pain, stiffness and swelling in the joints. It can lead to chronic disability and reduced life expectancy. Previous treatment options left almost half of patients with symptoms of continuing disease, deterioration of physical function and progressive joint damage.
In a series of experiments using tissue taken from joints, Maini and Feldmann investigated the role of cytokines – protein messenger molecules which drive inflammation – and found that a number of pro-inflammatory cytokines were present in the inflamed joints. However they found that a single cytokine, TNF, was capable of driving the disease process. This led them to seek ways of proving this concept in patients, using a monoclonal antibody to block TNF.
The first clinical trial was performed in 1992 and revealed rapid and dramatic improvement of rheumatoid disease activity with anti-TNF therapy. The successful clinical trials in the UK, further claims for more exploratory trials within Europe and USA led to the development of three anti-TNF drugs – infliximab, etanercept and adalimumab. These drugs are effective in about 70% patients with severe disease, even those resistant to all previous treatment. Most importantly this new class of drugs protect the joints from further destruction.
As TNF is also involved in other chronic inflammatory diseases, their pioneering work has led to anti-TNF therapy being used routinely for Crohn's inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis as well as for children with chronic arthritis (such as juvenile idiopathic arthritis). The discovery of anti-TNF also spawned a host of other biological therapies for inflammatory arthritis.
Maini and Feldmann have been recognised for this work on previous occasions, having been awarded the Albert Lasker Award for Clinical Medical Research in 2003, and the Crafoord Prize of the Royal Swedish Academy of Science in 2000. Both also received knighthoods in recognition of their achievements.
Professor Sir Ravinder Maini, now visiting professor at the Kennedy Institute of Rheumatology at the University of Oxford, commented: “The discovery that inhibiting just one molecule could make such a huge difference to the many sufferers of this terrible disease was a truly remarkable find. It is extremely pleasing to find our research has benefited so many, and has been recognised through this award.”
Professor Sir Marc Feldmann, now head of the Kennedy Institute, added: “We welcome the presentation of this award, and it is an absolute pleasure to see that well funded long-term research such as that supported by Arthritis Research UK can have such benefit for patients on a global scale. The strength of our research that we were able to develop enabled us to influence the pharmaceutical industry to take a bold step and move into new territory, which proved to be very fruitful for those suffering with rheumatoid arthritis".