Are you a Health Professional? Jump over to the doctors only platform. Click Here

What triggers rheumatism?

Print Friendly, PDF & Email

Why does one person with inflamed joints develop rheumatism, while in another person the disease disappears? And why do some people respond well to medication while others do not? An interdisciplinary European consortium with LUMC as initiator and co-ordinator will be studying how the biological processes underlying these questions work.

Paradigm shift in treatment

The basic premise of this research is not that rheumatism is an untreatable condition. Quite the contrary: rheumatism – the official name for this chronic inflammation of the joints is rheumatoid arthritis – is one of the success stories of modern medicine. ‘When I started, rheumatism was a terrible disease,’ says Huizinga, who obtained his PhD in 1989. ‘People soon became invalids and died at an earlier age than non-sufferers. But in recent years there has been a paradigm shift in the treatment of the disease: rather than waiting until sufferers develop chronic rheumatism, we now treat the condition at a much earlier stage. And the results so far are promising. You still can’t talk of a cure, but periods of remission when medication is not needed are possible. Rheumatism is a common disease; 1% of the population has it. But it’s less visible these days as a result of effective medication.’

What is rheumatism?

‘The next step is to treat the activity of the disease in a structured way,’ he continues. What do you do, for example, if a patient responds well? Do you carry on with the medication, or do you stop? To make such a decision you need to know what is going on in the body, and we still don’t know enough. What exactly is rheumatism? Of the people who come to the clinic with undifferentiated arthritis, for example inflamed joints in the fingers, most (40 to 50%) do not develop rheumatism. This group is an interesting focus of study.’

Prediction model

The Leiden rheumatologists have already developed a prediction model with a points system for contracting rheumatoid arthritis, which has been validated worldwide. Huizinga: ‘According to this model, the probability increases is you are female or older, if you have a particular inflammation of the joints, if you have rheumatoid factors in the blood and if you have auto-antibodies in your blood. Rheumatism is clearly an auto-immune disease. We understand very little of the differences between men and women, although a lot of research is being conducted in this area. Ageing processes are also not yet well understood. That leaves three things. In these three processes a kind of ‘mains switch’ goes on which causes the joint inflammation to become chronic, and you then have rheumatoid arthritis. When the call for proposals came from the EU’s Seventh Framework Programme for research projects into early processes of inflammatory diseases, I and biologist and rheumatism researcher René Toes, who was awarded a Vici subsidy at the end of last year, looked for the very best groups in Europe and wrote a research project.’


Biomarkers

The aim of the project, for which the consortium has 11 million euro available, is to determine the relevant biomarkers for the ‘switch points’, and then to understand and influence the underlying processes. In other words: to establish drug targets. ‘The advantage of European co-operation is that there are large numbers of patients and control subjects. There are also 200 different transgenic and knock-out mice available, so that you can influence the variables in a structured way. To integrate the huge amount of data you also need bioinformatics. Once you have put all this together, you are one step nearer.’ The consortium will be studying processes at different levels, from the molecule to the whole organism. There is also a continuous interchange with clinical practice. As well as research institutions, biopharmaceutical companies are also represented.’

European co-operation

As a scientist, it’s generally better to work within a small group,’ says Huizinga. ‘In the first instance you think: these megalomaniacal projects are a challenge mainly for your management skills. On the other hand, rheumatism is a significant problem for society, so society has every right to expect you to pool your resources and skills, to arrive at better insights and treatments. I am a doctor for 50% of my time and a scientist for the other 50%. It certainly keeps me busy. I am a good organiser, but I have no legal skills and no knowledge of the specific management requirements and financial rules of the EU. The expertise of LURIS is crucial here, as is the co-operation with the research directorate and the financial service of the LUMC.’
On Saturday 7 February, Huizinga was presented with the Willy van Heuman prize of the Stichting Stimuleringsfonds Alternatieven voor Proefdieren. In partnership with knowledge institute TNO, he has developed a new animal-free model for rheumatism to study processes at cell level. Huizinga: ‘Animal research is and will remain essential; people and animals are so complex – and also they are so cleverly put together – that we can’t do without them. But that does not alter the fact that you have to keep animal experiments to an absolute minimum.’

(Source: Leiden University: Mechanisms to Attack Steering Effectors of Rheumatoid Syndromes With Innovative Therapy Choices: March 2009)


Print Friendly, PDF & Email

Dates

Posted On: 16 March, 2009
Modified On: 16 January, 2014

Tags



Created by: myVMC