Ryback et al. (2026)
- Authors: Audrey A Ryback, Charles B Hillier, Camila M Loureiro, Chris P Ponting, Caroline F Dalton
- Institutes: MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK, Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK, Department of Neurosciences and Behaviour, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Publisher: PLOS ONE
- Link: DOI
Summary
This high-quality replication study challenges the hypothesis that ME/CFS is caused by circulating blood factors that directly impair energy production in muscle cells. By showing that healthy muscle cells behave normally when exposed to patient serum, the research suggests that metabolic issues in ME/CFS may be more complex or specific to the patients’ own cellular environment. These findings help the scientific community narrow down where to look for the true cause of the disease by ruling out a previously suspected mechanism.
What was researched?
This study investigated whether serum from patients with ME/CFS contains circulating factors that alter mitochondrial function and energy metabolism in healthy muscle cells.
Why was it researched?
The research was designed as a large-scale replication of earlier findings which suggested that ME/CFS serum could trigger abnormal mitochondrial respiration in healthy cells, potentially serving as a diagnostic marker.
How was it researched?
Researchers conducted a pre-registered study using serum from 67 ME/CFS patients and 53 healthy controls to treat cultured healthy myoblasts. They utilized a Seahorse Bioanalyser to perform over 1,700 mitochondrial stress tests, measuring oxygen consumption and metabolic activity with high precision.
What has been found?
The study found no significant differences in mitochondrial phenotypes or respiration rates between muscle cells exposed to ME/CFS serum versus control serum. The primary measurement of interest, the oxygen consumption rate at maximal capacity, was indistinguishable across both groups.
Discussion
The results provide strong evidence against the theory that circulating factors in ME/CFS blood consistently impair the mitochondrial performance of healthy muscle precursor cells. The study’s large sample size and rigorous methodology suggest that previously reported differences may not be generalizable to the broader ME/CFS population.
Conclusion & Future Work
The authors concluded that the metabolic dysfunction observed in ME/CFS patients is likely not driven by universal factors circulating in the blood. Future research should focus on other biological compartments or different cell models to identify the specific drivers of the disease.