Assistant Professor Rob Wüst of Vrije Universiteit Amsterdam has been awarded a grant from the Netherland’s ZonMw for his research project entitled, ‘From sick to sicker with exercise: deciphering the base of post-exertional malaise in post-COVID’. In addition, ZonMw is also funding four additional research projects involving Prof Wüst as a co-applicant.
(photo by Patrick Siemons)
The funding is in part implementation of a 28.5 million euros 10-year programme under the Dutch Minister of Medical Care and Sport, Tamara van Ark’s, 2021 direction to ZonMw to carry out a biomedical research programme on ME/CFS, which has already seen a grant in excess of seven million euros being awarded to Amsterdam University Medical Centre (Amsterdam UMC) with a further 4 million euros for a second consortium in UMC Groningen.
Prof. Wüst’s new research aims to identify which specific muscle cells are involved in the pain and fatigue that arise during Post Exertional Malaise (PEM) in people with long COVID. Of course, PEM is also a cardinal symptom of ME/CFS and so the results will be of interest to ME/CFS researchers. His research will look at how the body — particularly the blood, immune cells, and central nervous system — responds to exertion in post-COVID patients and, by so doing, hopes to gain greater insight into how PEM symptoms develop. Researchers also anticipate that their studies may aid the development of tests which can more accurately diagnose PEM and provide insights for treatments that could help patients build strength and reduce the duration of PEM symptoms.
As co-applicant, Prof Wüst will also be working on the other 4 projects funded by ZonMw.
- A project exploring the development of a metabolism-targeting drug that is now entering phase 2, building on previous research by VU Amsterdam and Amsterdam UMC.
- Cell culture experiments studying autoimmunity in cells, including muscle cells.
- Use of heart rate variability as a means of monitoring exertion in post-COVID patients, in collaboration with several sports physicians in the Netherlands.
- A clinical trial focusing on autoimmunity.
Their findings may help improve our understanding of PEM in ME/CFS, and possibly pave the way towards new therapies.
Prof Wüst has delivered the outcomes from previous work at both the Unite to Fight Conference and Invest in ME Research Conference. At the latter he presented his findings on muscle changes in individuals with long COVID, and emphasised how counterproductive exercise can be for individuals with the illness, and for those with ME/CFS, especially beyond the “post-exertional malaise (PEM) threshold”. His research revealed that there were fewer red muscle fibres in people with long COVID, and that amyloid-containing deposits/“clots” increased post-exercise. Additionally, the team conducted a study where 60 healthy individuals underwent 60 days of bedrest in order to induce deconditioning. The findings suggest that the muscle changes seen in healthy participants with induced deconditioning are not the same as those observed in studies looking at people with ME/CFS – indicating that deconditioning alone does not explain ME/CFS symptoms.
During the Q&A, at the Invest in ME Research Conference an audience member hailed Prof Wüst’s research as “one of the most significant contributions in the past 12 months.”
Prof Wüst’s ZonWm-funded projects dovetail nicely into his ME Research UK-funded work. Very little is known about the causes of muscle abnormalities and PEM in ME/CFS but given the similarity in symptoms and potential link between ME/CFS and long COVID, could there be a biological similarities in both? Prof Wüst and colleagues will assess muscle biopsy samples taken from people with ME/CFS before and after inducing PEM. Immunofluorescence techniques will be used to identify and assess the location of microclots in the muscle and in blood samples, and to correlate these with the presence of clinical symptoms. Electron microscopy will also be performed to assess the structure of the capillaries (microscopic blood vessels) and mitochondria (responsible for energy production in cells) in the skeletal muscle fibres. A third aim is to look for markers in the blood that indicate muscle tissue stress, and to determine whether these correlate with abnormalities in muscle tissue structure.
Understanding the clinical consequences of PEM will not be possible without a better comprehension of the pathological mechanisms involved, and the researchers anticipate that their findings will help do this.
The results of Prof Wüst’s ME Research-UK funded work will be integrated into the newly developed Netherlands ME/CFS Biobank and Cohort, and may pave the way towards a new therapy which, if it is based on established treatments, could be implemented relatively quickly.
News of Prof Wüst’s grant success comes as it is announced that from 1 November 2024, the first post-COVID centres of expertise will open their doors in the Netherlands. Maastricht, and Amsterdam University Medical Centres, and Erasmus Medical Centre will be the first to begin operation with others following thereafter. A post-COVID centre for children is currently being established by UMC Utrecht, Amsterdam UMC, and Maastricht UMC.
