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Arthritis Research: Britain's Role
by John Newell
Former Science Editor, BBC World Service

"Britain should be proud and immensely grateful for the achievements of arthritis research over the last 60 years, They are bringing direct benefits to sufferers throughout the world." So said Paul Dieppe, Professor of Rheumatology and Dean of the Faculty of Medicine at the University of Bristol, in a recent review of research into arthritis in progress in the United Kingdom commissioned by the British charity the Arthritis and Rheumatism Research Council (ARC), which supports much of the research in the UK.

The ARC believes the review shows that Britain leads the world in terms of arthritis research. Professor Dieppe lays special emphasis on exciting new British work on enzyme inhibitors and monoclonal antibodies being developed to control the causes of rheumatoid arthritis.

He says that researchers are sometimes criticised for having failed to find "The cure" after 60 years of research supported by the ARC. But while it remains true that many forms of arthritis are still incurable, they are no longer untreatable. The improvements in the care and likely outcome for most people with arthritis have been spectacular, and research has led to genuine optimism that more cures will soon be forthcoming.

We now know that there are 200 different types of arthritis. They have been defined through painstaking observational research.

"The importance of this cannot be overest imated, " says Professor Dieppe. "We can only begin to find the causes and cures if we first understand the different types of disease that we are dealing with."

One way to discover the cause of disease is to document the frequency and distribution of the different forms in which it occurs. This is known as epidemiology.

"ARC had the foresight to set up an arthritis epidemiology research unit, in Manchester, many years ago," says Professor Dieppe.

Different Forms
The length of time for which this unit has been collecting data has enabled it to collect some extremely valuable information about the distribution of different forms of arthritis, which has given valuable clues to their causes.

Another form of social rather than laboratory research into arthritis which has been largely pioneered in the UK has been research into the impact of the disease on society.

"We can now provide our politicians and health leaders with well-documented evidence that arthritis is one of the most important health problems in our society, that it is growing in significance as the population ages, and that it is a huge cost burden to the country. We have also collected sobering data about the numbers of people in pain or disabled," says Professor Dieppe.

This sort of data is of value far beyond the UK, since although the details are different, the social changes and problems brought about by ageing populations are being felt in many ageing populations.

Growing Cost
The huge and growing cost burden of arthritis revealed by British surveys provide the springboard and justification for other surveys in other countries, as well as providing valuable predictions to help in deciding national caring and research budgets and priorities.

For some common forms of arthritis, including gout and some occupational forms of osteoarthritis, research has already revealed the causes, along with ways of life or procedures which can help to avoid the development of disease.

Gout is now safely controllable using allopurinol. For other forms of arthritis, research to identify causes continues. "We have 200 different joints in our bodies" says Professor Dieppe, which are constantly in use for over 70 years, far longer than any machine. As well as asking why they go wrong, we need to ask what normally maintains them in reasonably good condition, in spite of treatment that would wear out any machine.

The answers to these questions are valuable in more than one direction. On the one hand discovering the body's normal repair and maintenance mechanisms gives hope of becoming able to stimulate them artificially when they fail to work properly in arthritis. On the other hand studying the properties of living joints can provide lessons for the designers of mechanical joints of all kinds, as well as for those bioengineers who are specifically concerned with the design of artificial joints, such as hip joints, to replace natural joints that have finally worn out.

Tissue Repair
Two natural processes are crucial to maintaining the normal integrity of our joints; inflammation and tissue repair. It is now clear, thanks largely to British research at centres such as the Kennedy Arthritis Research Centre and the Postgraduate Medical School in the Hammersmith Hospital in London, that the key mechanisms of rheumatoid and osteoarthritis are abnormalities of inflammatory and repair processes respectively.

Inflammation is the main means used to get rid of microbes and foreign bodies that may enter the joints. It is probably normally crucial to joint health. But in rheumatoid arthritis the process gets out of hand.

"Great strides have been made" says Professor Dieppe. "In our understanding of this process, leading to new strategies in controlling it."

It is also worth mentioning that parts of the sequence of events by which inflammation causes damage in rheumatoid arthritis appear to be identical to those by which similar processes cause damage in other auto-immune diseases, including multiple sclerosis and forms of diabetes and thyroid disease. Thus research on, and even perhaps treatments developed for one of these conditions may prove valuable and effective for others.

Similarly the roughening and pitting of cartilage found in osteoarthritis is normally prevented by repair mechanisms which fail in the disease condition. Over the last few years research, much of it carried out by Professor Dieppe himself, has led to exciting new ideas about how we might restore normal repair mechanisms in joints, and stimulate cartilage to heal better.

Genetic Factors
British groups were among the first to link specific genes to susceptibility to forms of arthritis (ankylosing spondylitis to the B 27 gene and rheumatoid arthritis to the DR 4 gene.) Not only can such genetic markers potentially be used to provide tests for abnormal susceptibility, which can then be used to reduce risks and effects by the adoption of an appropriate lifestyle. There is also, says Professor Dieppe, the more distant possibility "of developing ways to neutralise harmful genes, and even of developing forms of gene therapy. "

Several laboratories in the UK, notably within the Kennedy Institute, are well advanced with the development of monoclonal antibodies designed to react with and to "switch off" the immunological processes behind the development of systemic lupus erythematosis as well as rheumatoid arthritis.

Others are developing the use of anti-cytokines, such as anti-TNF (tumour necrosis factor) to neutralise the chemical messengers that drive the inflammatory process. Others again are developing enzyme inhibitors that can block the action of chemicals that otherwise cause the erosion of bones and joints.

"Many experts think we are on the threshold of a new leap forward in the treatment of rheumatoid arthritis either through the progress of British work on anti-TNF or through the genetic work that is revealing the causes of the disease through enzyme inhibitors or the development of monoclonal antibodies," says Professor Dieppe.

"Throughout the development of arthritis research in the UK has been one of the major contributors. There are more than 400 ongoing research projects on arthritis in the UK currently funded by the Arthritis and Rheumatism Research Council."

For more information contact:
Arthritis and Rheumatism Council
P.O. Box 177, Chesterfield, United Kingdom, S41 7TQ
Tel: +44 01246 558033 | Fax: 01246 558 007      Copyright ©1999, LLC