Biomedical aspects of ME/CFS studied by 2 consortiums

'We each have a different angle, but we will also complement each other’, says consortium manager Dr. Jos Bosch of the University of Amsterdam and Amsterdam UMC. Professor Judith Rosmalen of UMC Groningen, who heads the other consortium, adds, 'We will be organising a lot of things together, including for and with patients. As soon as we have results we’ll announce them jointly. And we’ll also be organising joint activities for the researchers in the two consortiums.'

2 consortiums have been set up to tackle the complex puzzle that is ME/CFS. The consortium led by Rosmalen uses Lifelines, a large population study launched in the northern Netherlands back in 2006, monitoring the health data of no fewer than 167.000 people. The subjects also complete questionnaires and attend a research facility once every 5 years, where tests are performed, including a lung function test, and biomaterial samples such as urine, blood and hair are taken.

‘Criteria for diagnosing ME/CFS were included in Lifelines data collection almost 10 years ago', says Rosmalen. ‘So we have lots of biomedical information and biomaterials from patients with ME/CFS. This also enabled us to find people with ME/CFS who had not been diagnosed yet. We plan to compare all these patients in a variety of ways with healthy Lifelines participants, or participants with other chronic diseases like multiple sclerosis. And we can also look back, to identify biomedical changes in people who went on to develop ME/CFS. Hopefully, that will give us ways of developing better diagnosis and treatment methods.'

This consortium’s greatest strength lies in the large quantity of data and materials already available. The consortium itself will also gather extra biomaterials and data. Faeces will be collected to see what bacteria people have in their gut (microbiome). It will also study the effects of intense physical and mental exertion on performance, the metabolism and processes in the brain. All the biomaterial gathered will be used to analyse the genetic background to ME/CFS, as well as immune response. ‘There is, for example, evidence that antibodies against certain bacteria are more prevalent in people with ME/CFS’, Rosmalen explains. ‘One of our researchers showed this in a relatively small study. We can now test this in lots more patients.'

‘We took our lead primarily from the ME/CFS research agenda’, says Bosch. This document sets out what criteria the new ME/CFS research programme needs to meet, according to patient groups. ‘The agenda also stresses that housebound and bedridden patients should also be involved in research’, he continues. ‘The most seriously affected patients are often overlooked by researchers.’ So patients will be visited at home by specially trained nurses. If extra tests are needed, like a scan at a research facility, patients will be given help with transport and accompanied if necessary. The NMCB consortium will also pay home visits to patients who want to participate in one of the studies being performed by the ME/CFS-Lines consortium.

‘We invite patients to take part in the NMCB cohort through patients’ associations, their own networks, GPs, hospitals and specialist clinics’, Bosch tells us. ‘Scientists from all the university medical centres are involved in the study, as well as specialist clinics like Cardiozorg and the Vermoeidheidskliniek (Fatigue Clinic), where lots of people with ME/CFS go.'

‘We have harmonised our methods and procedures with other international ME/CFS cohorts, like those in the United Kingdom, Germany, the United States and Canada.’ This means that data can be exchanged on a large scale at a later stage, and that’s a huge benefit. ‘We know that this approach is more likely to lead to reliable, usable results’, says Bosch. ‘That will allow ME/CFS research in the Netherlands to progress more quickly.’

At national level, Bosch links ME/CFS research with research on long-term conditions after infection, such as post-COVID, Lyme disease and Q fever. Some of these patients meet the ME/CFS criteria. ‘We work with the National Institute of Public Health and the Environment and others who are tracking thousands of people with post-COVID and Lyme disease. So existing cohorts have already yielded a lot of data, says Bosch. ‘The NMCB is building and expanding on that with ME/CFS diagnostics and extra data collection. That could provide some important insights into the onset of ME/CFS and the mechanisms responsible for post-infectious syndromes.

‘We’ve managed to bring together researchers from a range of biomedical research fields and institutes in this consortium. The Netherlands had invested very little in biomedical research on ME/CFS, but there was a lot of interest among researchers. Thanks to this ZonMw programme lots of them are now working together.’

The ZonMw ME/CFS research programme came about partly thanks to the active role played by patients and their representatives. Patient organisations also have an important role in both consortiums. 'We’re working closely with ME/CVS Nederland’, says Rosmalen. ‘Their chair Theo Kuiphof is a member of our steering committee, which also includes the 4 project managers and myself. The foundation had a lot of input into our project proposal, and we’re now looking together at how they will contribute to the implementation.'

'Patient organisations were closely involved in shaping the NMCB proposal’, says Bosch. ‘ME/CVS Nederland, the ME/cvs Vereniging and the Steungroep ME en Arbeidsongeschiktheid are all represented on the consortium’s board. Patients and their representatives are also on the advisory committee, and are represented in the teams performing the six individual studies. I think they play a very important role, both in terms of substance, and of keeping the researchers focused. They will also ensure that the results are put into practice quickly.'

‘Though we would like to get there more quickly, it takes time to find an effective treatment ', says Rosmalen. 'If everything goes better than expected, we could have a place to start in 4 years’ time. Then you might be able to see whether existing medications that have already been safety-tested can be studied in patients.'

‘ME/CFS probably has several causes, and there are various subtypes’, explains Bosch. ‘A drug or other treatment that works on one group of patients might not work for everyone. It takes time to identify that kind of thing.'

The 2 consortiums are therefore focusing on training a new generation of researchers, in the hope that biomedical research on ME/CFS will become stronger and more successful. Ultimately, it’s about ensuring that every patient with this debilitating illness gets effective treatment.

text: Pieter van Megchelen | images: Lilian van Rooij | translation: Sue McDonnell Translation.