Arthritis Research Campaign scientists receive Lasker Prize for discovering new treatment for rheumatoid arthritis
Two of Britain's leading biomedical researchers Emeritus Professor Sir Ravinder "Tiny" Maini and Professor Marc Feldmann have received the prestigious 2003 Albert Lasker Award for Clinical Medical Research for their discovery of anti-TNF (tumour necrosis factor) treatment as an effective treatment for rheumatoid arthritis and other related diseases.
The Lasker Awards for basic clinical and medical research have come to be known as 'America's Nobels' and 66 recipients of the Lasker award have gone on to receive Nobel prizes. They were first awarded in 1946.
It is only the third time that rheumatology research has been honoured with a Lasker Award. The first was for the discovery of corticosteroid in 1949; the second for joint replacement surgery in 1974, and anti-TNF treatment is the third.
Professors Maini and Feldmann, both based at arc's flagship institute, the Kennedy Institute of Rheumatology, a division of Imperial College London's Faculty of Medicine at Charing Cross Hospital, began working together 20 years ago to establish which molecules in rheumatoid arthritis were driving the inflammation and joint destruction, seeking new avenues of treatment. Their research was funded by long-term core support by arc and involved a team of scientists and clinicians.
Rheumatoid arthritis is a chronic inflammatory disease affecting the immune system. It affects about 387,000 people in the UK, causing much pain, and progressive joint damage leading to chronic disability and reduced life expectancy. Previous treatment options still left almost half of all patients with symptoms of continuing disease, deterioration of physical function and progressive joint damage.
In a series of experiments using tissue taken from joints, Feldmann and Maini investigated the role of cytokines, protein messenger molecules that drive inflammation, and found that a number of proinflammatory cytokines were indeed 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, and through collaboration with an American biotech company, used a monoclonal antibody to block TNF.
Their first clinical trial was performed in 1992 at Charing Cross Hospital and revealed rapid and dramatic improvement of rheumatoid disease activity with anti-TNF therapy. This paved the way for a series of larger European and US trials proving the effectiveness of TNF blockade, and leading to the development of three anti-TNF drugs, infliximab, etanercept and adalimumab. These drugs are effective in most patients, even those resistant to all previous treatment. Most importantly this new class of drug protects the joints from further destruction.
This research has had a major impact, providing new and effective treatment for resistant rheumatoid arthritis patients benefiting almost 500,000 worldwide. Although these drugs have been found to be cost effective by NICE (National Institute for Clinical Excellence), a recent report from the Arthritis and Musculoskeletal Alliance, the umbrella body that represents arthritis charities and bodies in the UK, suggests that not all patients who qualify for this £10,000 per year treatment in the UK are receiving it.
As TNF is also involved in other chronic inflammatory diseases, Maini and Feldmann's pioneering work has led to anti-TNF therapy being used routinely now for Crohn's inflammatory bowel disease, psoriatic arthritis, ankylosing spondylitis as well as for children with chronic arthritis. Many other diseases have also responded to anti-TNF therapy in early stage clinical studies. It is now evident that monoclonal antibodies such as infliximab that Maini and Feldmann used with success can also be employed long-term, and problems anticipated with injecting antibodies chronically can be overcome, especially if immunosuppressive drugs such as methotrexate are used in conjunction with it.
Feldmann and Maini were also been honoured by the award of the Crafoord Prize of the Royal Swedish Academy of Science in 2000.
Sir Ravinder comments: “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 Feldmann comments: “It is a great honour to receive this award, and a pleasure to see that well funded long-term research such as that supported by arc at the Kennedy Institute can have such benefit for patients. The research strength we were able to develop enabled us to influence the pharmaceutical industry to move into new territory, which proved to be very fruitful".
Fergus Logan, chief executive of arc says: "This award is open to all medical specialties and all nationalities, so for UK rheumatologists to win it is a significant achievement and shows that Britain punches above its weight in arthritis research - largely due to the generosity of our many supporters and our ability to continue to fund research into this group of diseases. The discovery of anti-TNF therapy is up there in the first rank of scientific discovery."
Professor Robert Winston, Director of Research and Development at Hammersmith Hospitals NHS Trust, and Professor of Fertility Studies at Imperial College London, says, “This is an excellent example of how close collaboration between academic researchers and doctors in the stimulating environment of leading academic hospitals can lead to major improvements in treatment for patients”.
