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.
Emeritus Professor Sir Ravinder Maini and Professor Marc Feldmann, both based at 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 the Arthritis Research Campaign (arc), and involved a team of scientists and clinicians.
Rheumatoid arthritis is a chronic inflammatory disease affecting the immune system. It affects about 400,000 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.
For this work, Feldmann and Maini have 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".
Professor Sir Leszek Borysiewicz, Principal of the Faculty of Medicine at Imperial College London comments: "This is a very significant award both for Marc and Ravinder, as well as for Imperial as a whole. It underlines the importance of translational research for the future of healthcare and is a fine example of how to take research from the laboratory bench to the patient's bedside in one seamless process."
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".
Emeritus Professor Richard Batchelor, of the Kennedy Institute of Rheumatology Trust, adds: "The concept of TNF-alpha being the key cytokine governing inflammatory reactions in rheumatoid joints, and other pathologically related conditions, was received with some doubts when first put forward by Drs. Feldmann and Maini and their collaborators in the '80 s. Such doubts were silenced by their further studies, culminating in the clinical trials that proved the striking and significant benefits of anti-TNF therapy. Huge numbers of patients throughout the world have already been helped by this important advance in treatment. The Albert & Mary Lasker Foundation Prize is a fitting award for this achievement."
Notes to editors:
1. Professors Maini and Feldmann will be presented with the 2003 Albert Lasker Award for Clinical Medical Research at a luncheon in New York City on Friday, 19 September.
2. The mission of the Albert and Mary Lasker Foundation is to enlarge public awareness, appreciation, and understanding of promising achievements in medical science in order to increase public support for research. The Foundation rests on the belief that only scientific investigation, and knowledge of basic human biology and disease processes, are the most reliable, efficient means by which to achieve prolongation of life and reduction in human suffering.
The centrepiece activity of the Foundation is an annual awards program, which recognises stunning achievements in basic and clinical research, as well as significant public service in behalf of medical science. The awards program serves to mark these milestones against disease and illness, and to create a venue for bringing to the attention of the nation's leaders and the general public the importance of medical science.
3. Consistently rated in the top three UK university institutions, Imperial College London is a world leading science-based university whose reputation for excellence in teaching and research attracts students (10,000) and staff (5,000) of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that enhance the quality of life and the environment - underpinned by a dynamic enterprise culture. Website: www.imperial.ac.uk.
4. The Arthritis Research Campaign (arc) is the fourth largest medical research charity in the UK, and in 2002 raised more than £26m to fund its extensive research programme. The Kennedy Institute for Rheumatology is the charity's flagship institute and is currently in receipt of £3.5m of funding a year.
5. NICE is the National Institute of Clinical Excellence, a part of the UK's NHS which helps to provide patients, health professionals and the public with authoritative, robust and reliable guidance on current best practice, which approved anti-TNF therapy for RA in March 2002.