Lost in translation? Not in Glasgow
Reproduced from Issue 132 of Arthritis Today
Translational research continues apace in Glasgow, aided by ongoing arc funding of £1.5m. Jane Tadman reports.
Professor Hilary Capell with a patient
The opening of a new biomedical research building at the University of Glasgow marks a major advance in scientific research in Scotland's second city.
As well as fostering exciting new possibilities in research into a variety of immunological diseases, the new building is a symbol of the increasing importance of links between basic and clinical scientists in the quest for new treatments and strategies. The university proudly talks of a new era of “cross-faculty development.”
All this sounds very impressive, but what does all this mean to people with arthritis? The answer is quite a lot. The ethos of arthritis research in Glasgow has always been that of translational research, in which the results of lab-based work have a direct effect on patients and their care. And while much of the funding currently comes from the Medical Research Council and the Wellcome Trust, arc 's infrastructure grants have been the glue that has kept the whole academic programme together for more than a decade.
Professor Iain
McInnes
One of the best people to explain this practical application of science is Professor Iain McInnes, whose laboratory group is now ensconced in the new biomedical research building, and who is both an immunologist and a consultant rheumatologist. His post has had the effect of acting as a bridge between laboratory research at the University of Glasgow and clinical research at the Centre for Rheumatic Diseases at Glasgow Royal Infirmary, where the arc Professor of Rheumatology, Roger Sturrock, heads up the clinical research team. Even the title, Professor of Experimental Medicine and Rheumatology, spells out this linking role very clearly.
“What's wonderful about Glasgow is that three essential things come together,” says Professor McInnes. “Firstly, there are the clinical rheumatologists, and the relationship between the NHS consultants and the academics is excellent. Secondly there is some very, very fine immunology-based science here, some really hard-core smart thinking scientists in a five star-rated unit, who use the resources of the rheumatology community. My appointment allowed the clinical interface between the clinical rheumatologists and strong, relevant, basic science. That juxtaposition has enabled us to ask some important questions.
“Thirdly, we have fantastic patients. Clinical research needs an enormous commitment from everyone and we need patients in our research. They're always very helpful and keen to get involved in trials and clinical studies.”
Combination drugs trial
One way in which patients have been invaluable in clinical research, and in turn, have benefited directly from it, is the MASCOT trial, run by one of Professor McInnes's clinical colleagues, Professor Hilary Capell, and funded by arc over a six-year period at a cost of more than £250,000. The trial didn't test the effectiveness of exciting new biologic therapies but rather the so-called bread and butter everyday drugs used to treat the vast majority of rheumatoid arthritis (RA) patients – sulfasalazine and methotrexate.
Professor Capell wanted to discover if patients who didn't respond particularly well to taking sulfasalazine would benefit from changing to methotrexate, or from taking both drugs in combination.
The trial of almost 700 patients in the west of Scotland showed that those patients on combination therapy did better than those on either sulfasalazine or methotrexate, and that patients did not experience either more side effects or toxicity.
Professor Capell said that a great deal was known about the two drugs and their safety profiles, and that achieving a better response with widely available therapies was important. “The fact that almost a third of patients did well on sulfasalazine and didn't need to take it in combination, suggests that a ‘step-up' approach should be used with RA patients,” she added. “The message from this trial is that two drugs are better than one in appropriately selected patients, and also that we need to manage patients more proactively, changing their drugs sooner if they don't work.”
Exciting potential therapies
Professor Roger
Sturrock
The emphasis on translational research has been behind two of the most significant developments in immunology in Glasgow in recent years.
Professor McInnes and colleagues discovered that a cytokine called Il-15 present in the joints could be blocked in model systems, leading to a reduction of symptoms in inflammatory arthritis. The research has now been taken on by commercial partners with a view to Il-15 being developed as a potential new drug, which he describes as “enormously exciting.”
The west of Scotland has a particularly high prevalence of heart disease, and studies in Glasgow on the links between heart disease and RA a few years ago discovered that cholesterol-lowering drugs called statins can play a part in reducing the risk of heart disease in RA patients. Many of the markers of heart disease risk were very favourably changed by statin treatment and a small clinical trial also showed that statins offered a modest benefit. (click here for news of a major new £1m arc /British Heart Foundation trial of statins in RA).
Coming right up to date, Professor McInnes is bubbling with enthusiasm about the potential of current research to take treatments beyond anti-TNF therapy.
Anti-TNF therapy – and beyond
“Rheumatology, immunology and cardio-vascular researchers are all together now in the new building, and there are several extraordinarily exciting things happening at the moment,” he says. “TNF drugs are really effective in 70 per cent of patients but 30 per cent don't respond or lose the effect, so there is still an unmet clinical need; this is my mantra. If anti-TNF was the end of the story of new treatments for inflammatory arthritis we would be letting our patients down. If we regard it as the beginning of the story, it's an outstanding advance.”
Rather than talking about finding a possible cure, Professor McInnes says that researchers in Glasgow are now turning their attention to the possibility of inducing remission, or what he describes as immunological remission.
“In clinical remission, patients feel better while taking medication. In immunological remission the patient feels better when the treatment is withdrawn. It's like having an immunological thermostat which re-rights the balance of the immune system and everything goes back into a state of equilibrium. It's a more subtle intervention that will leave the rest of the immune system unaffected.” Watch this space for further developments.
What else is arc funding in Glasgow ?
Childhood arthritis
Dr Janet Gardner-Medwin
arc is helping to establish the relatively new specialty of paediatric rheumatology north of the border by funding Dr Janet Gardner-Medwin, Scotland's very first full-time children's arthritis specialist. Based at the Royal Hospital for Sick Children at Yorkhill, with an academic base at the University of Glasgow's Department of Child Health, she holds the post of arc senior paediatric rheumatologist, and is helping to develop a network of specialist clinics around the country, so that youngsters no longer have to travel long distances for treatment in Glasgow .
Dr Gardner-Medwin and clinical colleagues Dr Paul Galea and Dr Joyce Davidson are extending childhood arthritis outreach clinics to Falkirk, Stirling, Inverness and Dumfries. The plan is that once adult rheumatologists or paediatricians are trained, 90 per cent of children with arthritis can be treated in their local hospital, with only severe or unusual cases having to come to Yorkhill.
Dr Gardner-Medwin is also running collaborative research projects examining the risk of heart attack and stroke in young people who develop arthritis during childhood, looking at the role of different imaging of the joints in predicting disease progression, and investigating the impact and mechanisms behind growth abnormalities associated with childhood arthritis.
The first in a new fellowship scheme to encourage research into childhood arthritis has been awarded to another children's arthritis expert in Glasgow. Dr Orla Killeen, a specialist paediatric registrar has a six-month Barbara Ansell Fellowship to find out if it is possible to identify the future severity of the condition of a child with newly diagnosed juvenile idiopathic arthritis. (Click here for more information)
Orthopaedic research
Over at Strathclyde University, bioengineer and arc non-clinical lecturer Dr Nicola Fowler has been developing a “virtual surgery” tool to improve the success of hand and wrist surgery in patients with RA. Nearing the end of the two-year research project, Dr Fowler expects the results of her research will improve prosthetic design and the soft tissue reconstructive procedures used by surgeons to correct deformities caused by RA.
In a separate project she is also evaluating the various surgical treatments of wrist problems, and finding out more about the mechanisms of wrist joint instability.
At Glasgow University's Dental School, Dr Marcello Riggio is investigating why, out of the 75,000 hip replacement operations carried out every year, more than 1,000 fail because they become infected and have to be revised. Current knowledge of why this happens is poor, and Dr Riggio, a senior lecturer in molecular microbiology, aims to determine the types of bacteria that are in the joint and the way the infections start.
Education
Dr Max Field, at the Centre for Rheumatic Diseases at Glasgow Royal Infirmary, has an educational project grant to train fourth year medical students become future trainers, using up-to-date teaching methods to train junior colleagues and improve their ability to examine the musculoskeletal system.
Hypermobility
Bill Ferrell, Professor of Clinical Physiology at the Centre for Rheumatic Diseases, has discovered that reflexes at the knee joints were missing in almost half the people with hypermobility studied. But after undertaking a home-based exercise programme, patients regained their reflexes, thus providing scientific evidence of the benefits of exercise in this condition.
Ultrasound
Ultrasound is a useful and increasingly used way of examining the musculoskeletal system to detect problems with muscles, tendons, ligaments, joints and soft tissue. The Centre for Rheumatic Disease set up the first ultrasound musculoskeletal unit within a rheumatology department in Scotland, with arc funding to buy equipment, swiftly followed by an arc education project grant to Dr David Kane, PhD student Dr Peter Balint and Professor Sturrock. This resulted in the production of a DVD for beginners, a handy learning tool aimed at rheumatologists and other musculoskeletal practitioners who want to train in musculoskeletal ultrasound.
“Ultrasound is the rheumatologist's stethoscope,” said Professor Sturrock. “It's used more and more for diagnosis and monitoring treatment in all kinds of arthritis from RA to soft tissue problems and tennis elbow.”
