Focus on St Thomas's, London
Thames gateway to research
Reproduced from Issue 133 of Arthritis Today
Ongoing research into the genetic basis of osteoarthritis could lead to improved treatment for people with severe disease. Jane Tadman reports.
To most people with severe osteoarthritis who are just struggling to get by, the idea that within a decade their condition could be taken as seriously as it deserves to be would be welcome news.
Imagine the following scenario: osteoarthritis patients are seen by a rheumatologist, and screened with a blood test and scanned to see if they are at risk of their condition progressing. Those with mild disease whose condition is not expected to get worse would be discharged, but those at high risk of their condition getting worse could then see a dietician and physiotherapist to discuss diet and exercise, and be offered the chance to go on a clinical trial to test new drugs. They would then have an annual check-up including an MRI scan to see if their condition had progressed.
Professor Tim Spector
This would be a fairly standard care pathway for a patient with inflammatory arthritis. In an ideal world it's what Professor Tim Spector, consultant rheumatologist at St Thomas 's Hospital, part of King's College, London, would like to see happen to osteoarthritis patients too. After all it's what happens in most other types of musculoskeletal conditions. But could it actually happen?
“Hopefully we will see new treatments in..…ten years' time”.
In order to answer that question Professor Spector draws a direct comparison with the way people with osteoporosis are now treated. “A proportion of osteoporosis patients get the condition severely – around one in four - similar to osteoarthritis. A lot of people have it, and are susceptible to it,” he says. “Within about five years of the invention of the DEXA scan (now used widely to measure bone mineral density) we had useful drugs, the bisphosphonates, whereas there had previously been no new drugs for 40 or 50 years. We now have a range of different, effective drugs for osteoporosis that reduce bone turnover, increase bone mineral density and reduce fractures.
“Once you develop a test like that for osteoarthritis that can select people at the highest risk of their condition worsening and measure them accurately, within a year or two many more products can be tested quickly and effectively. It will be another five years before MRI and ultrasound become real alternatives to x-ray and another five after that to test the drugs, so hopefully we will see new treatments in another ten years' time.”
As a rheumatologist who specialises in both osteoarthritis and osteoporosis, Professor Spector knows the importance of being able to predict and measure disease severity and progression. He recently co-ordinated the UK arm of a phase two and phase three trial of a bisphosphonate drug used in osteoporosis, on osteoarthritis patients. In the first smaller study of 300 women, the drug seemed to work well. In the larger study of 3,000 women, although it reduced markers of cartilage damage, it didn't alter x-ray changes. Professor Spector suggests that many of the women in the study had the sort of osteoarthritis that did not progress, so making it impossible – just using crude x-rays - to tell if the drug was working or not.
“A lot of people, probably about two thirds, have mild osteoarthritis that doesn't get any worse,” he says. “The remaining third do get worse. And these are the people we need to identify and target with new drugs. That's where the Chingford Study comes into its own.”
The Chingford Study
The Chingford Study, funded by arc since its inception in 1989, is a long-term observational study originally of 1,000 women from the town on the border of London and Essex, aged between 45 and 60, and set up by Tim Spector to identify risk factors for osteoarthritis and osteoporosis. Fifteen years down the line, with more than 650 women still on board, the study has yielded more than 70 journal publications and shed interesting light on how and why these conditions start, develop and progress. arc has just awarded a further £400,000 to take the study to completion in five years' time.
A Chingford Study volunteer undergoes a scan
There have been several major findings. One was that low grade inflammation may be a significant aspect of early osteoarthritis. Previously it had been thought that it was entirely due to wear and tear. Another was that there were definite links between osteoarthritis and osteoporosis, suggesting that bone turnover and repair are present in early osteoarthritis as well as in osteoporosis, and that osteoarthritis is as much a disease of bone as of cartilage. Hence the drug trials, testing osteoporosis drugs on osteoarthritis patients.
Professor Spector plays down a previous finding that hormone replacement therapy may protect against osteoarthritis, saying that evidence for this is now lacking, although there are certainly links between hormones and arthritis.
Research based on the Chingford Study women has also identified nine novel genes which are involved in the onset and progression of osteoarthritis. “As well as showing that certain genes predispose you to osteoarthritis, the genes you inherit can also determine how quickly the condition will progress,” explains Professor Spector. “Although there are many more genes to identify, we probably know of more genes for osteoarthritis than any other common disease.”
Scientists are close to developing a blood test for osteoarthritis
He believes that scientists are close to developing a single blood test to test for certain genes which would enable clinicians to establish which of their patients are more likely to have severe, progressive osteoarthritis. If this can be done, then his vision for how severe osteoarthritis patients should be treated could become a reality.
Tim Spector has been at St Thomas 's since 1996 and he and his team have conducted numerous arc-funded projects during that time. As director of the Twin Research Unit – housed in a unprepossessing cubby hole which boasts one of the best views in London looking across the Thames to the Palace of Westminster - he is a regular contributor to radio and TV health programmes, largely as a result of his twins genetic work. In the mid-990s he and his team showed that up to 65 per cent of osteoarthritis in the hands and knees was due to genetic factors – the first time that osteoarthritis had been shown to have a major genetic factor. Much of his research findings since have added to this knowledge, and the number of patients on the twin register has expanded vastly to more than 10,000. arc recently awarded a £100,00 grant to help maintain the musculoskeletal database. Dr Frances Williams currently has an arc project grant which aims to establish to what extent genetic factors are responsible for the progression of lumbar disc disease (also known as osteoarthritis of the spine) - the major cause of back pain.
Dr Deborah Hart, Professor Tim Spector and Dr Frances Williams
As well as his research and clinical trial remit, Professor Spector runs a regular osteoporosis clinic at St Thomas's, a vast, bustling mini-village of a hospital on Lambeth Palace Road, offering a “one-stop” service for patients who can be scanned, diagnosed and offered treatment in one appointment, also seeing particularly difficult-to-treat patients from outside London for tertiary referrals.
Asked why he is so interested in research into osteoarthritis, Tim Spector offers an honest response: “It was more interesting 15 years ago to do research into a disease which people knew almost absolutely nothing about. People made huge assumptions based on no knowledge at all, like it being a boring wear and tear disease. You can make much more of an impact than if you are working in a huge field like inflammatory arthritis, where you're just another researcher. And I've always been interested in the underdog!”
