Funded under the ME/CFS Consolidation Call 2026
Mechanism-based Reversibility Evaluation and Stratified Endophenotyping of Treatment Response in ME/CFS
Can the energy deficit in ME/CFS be reversed?
The research project ME-RESET at the Medical University of Vienna is studying 50 people with ME/CFS to find out where in the body the energy deficit arises and whether hyperbaric oxygen therapy can reverse it. It is led by Lukas Haider together with Kathrin Kollndorfer and Martin Krššák. ME-RESET builds on an earlier study and, like that study, is funded by the Vienna Science and Technology Fund (WWTF) and the WE&ME Foundation.
Why MRI scans often show nothing in ME/CFS
Many people with ME/CFS know this experience: after exertion, they feel worse for days. This worsening of symptoms is known as post-exertional malaise, or PEM. Several research groups have found signs that the energy supply of cells is disrupted during PEM. At rest, however, the brain and muscles usually look normal on MRI scans. The impairment only becomes apparent under strain, and strain is precisely what harms people with ME/CFS.
A test without physical exertion
Lukas Haider’s team is therefore taking a different approach. The participants do not exert themselves. Instead, they lie in the MRI scanner for about 30 minutes and breathe air with slightly less oxygen than usual. This roughly corresponds to the oxygen level at an altitude of 3,000 to 4,000 metres. A healthy brain responds by adjusting its metabolism.
Early findings from Vienna
In an initial study conducted in 2025 and 2026, the team used this test with 26 people with ME/CFS and 27 healthy controls. Even before the test, the brains of people with ME/CFS showed considerably higher levels of lactate. Lactate is produced when cells have to generate energy without enough oxygen. During the test, their metabolism also failed to adjust to the lower oxygen supply. The finding is preliminary: the group was small, and the paper is currently under review at a scientific journal.
Two questions ME-RESET aims to answer
Where does the energy deficit arise? Is too little oxygen reaching the tissues, or are the mitochondria, the powerhouses of the cells, struggling to use the oxygen available to them? To find out, the team will measure the metabolism of both the brain and the calf muscle under low oxygen. In the muscle, this is achieved with a cuff that is briefly inflated. The researchers will also run blood tests.
Can the impairment be reversed? All 50 participants will receive ten sessions of hyperbaric oxygen therapy at the Medical University of Graz. The team will take the same measurements before and after treatment. Half the participants will start treatment immediately, and the other half will start six months later. This also makes it possible to observe how the measurements change without therapy. Each participant will be examined three times in total, which also shows whether any effect lasts.
What is hyperbaric oxygen therapy?
During hyperbaric oxygen therapy (HBOT), patients breathe pure oxygen in a pressurised chamber. Studies on Long COVID and ME/CFS, including research from Graz and Charité in Berlin, provide initial evidence that the therapy may ease symptoms in some patients. Why it works and who it helps is not yet known. ME-RESET aims to answer exactly that.
Who is taking part in the study?
The study involves 50 people with mild to moderate ME/CFS. Three days of testing in Vienna and the course of treatment in Graz would be too demanding for people with severe ME/CFS. The advisory board, made up of people with ME/CFS and their family members, therefore explicitly advised against including them in the study.
People with ME/CFS helped design the study
The advisory board was involved in planning the entire study. On its recommendation, the team asks participants after each step how demanding they found it. The researchers also use FUNCAP, a questionnaire developed specifically for ME/CFS, to assess how well participants can manage everyday activities.
What the study could mean for people with ME/CFS
By the end of 2029, it should be clear whether the impairment can be measured, located and reversed. The findings could lead to an objective test for researchers to use in future studies to assess whether a treatment is working. Such a test could also show who benefits from the pressure chamber, sparing others a demanding therapy. The findings could also be relevant to people with Long COVID. Even a negative result is an important answer.
ap. Prof. Priv.-Doz. Dr. Lukas Haider
Neuroradiologist, Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna
Link to MMag. Dr. Kathrin Kollndorfer, Clinical Psychologist, Developmental and Interventional Neuroimaging Lab (DINLAB), Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna
Link to Assoc. Prof. Priv.-Doz. Mag. Dr. Martin Krššák, MR Physicist, Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna
Also funded under the Consolidation Call 2026: REVEAL-ME at the Medical University of Vienna. Matthias Wielscher’s team is investigating whether rare genetic changes contribute to ME/CFS in some people. Read more about REVEAL-ME
