Large-scale investigation confirms TRPM3 ion channel dysfunction in ME/CFS, 2025, Marshall-Gradisnik et al

John Mac

Senior Member (Voting Rights)
Full title: Large-scale investigation confirms TRPM3 ion channel dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease hallmarked by multiple systemic symptoms, including neurocognitive, respiratory, immunological, gastrointestinal and cardiovascular impairment that worsen following physical and mental exertion. ME/CFS is characterized by an elusive pathomechanism, profound impact on quality of life and an absence of diagnostic tests or evidence-based treatments. Transient Receptor Potential Melastatin 3 (TRPM3) ion channel has been suggested as a potential biomarker and target for therapeutics in people with ME/CFS, supported by a series of publications reporting genetic and protein changes. This study aimed to undertake a multi-site large-scale investigation to determine the consistency of TRPM3 ion channel dysfunction in people with ME/CFS.

Methods: TRPM3 ion channel activity was assessed in two distinct laboratory sites by independent investigators using whole-cell patch-clamp recordings performed in isolated natural killer (NK) cells from 36 ME/CFS participants characterized according to the Canadian Consensus Criteria and 42 healthy controls. The Mann-Whitney U test was used to compare endogenous TRPM3-like currents between cohorts. The effect of location was determined using a covariance analysis, while antagonist sensitivity was determined using Fisher's Exact test.

Results: Electrophysiological experiments revealed a significant reduction in TRPM3 function in NK cells from individuals diagnosed with ME/CFS compared with controls in all parameters analyzed. Importantly, there was no significant effect of the laboratory sites on the results of this investigation, which confirms TRPM3 as a consistent biomarker for ME/CFS.

Conclusion: The current large-sample-size study confirmed previous results regarding TRPM3 ion channel dysfunction in NK cells in ME/CFS, demonstrating involvement of TRPM3 in the pathomechanism of this condition. Therefore, this multiple-site investigation offers strong evidence demonstrating TRPM3 as a potential biomarker for the diagnosis of ME/CFS, given the accumulating evidence.

 
Does anyone knowledgable have any opinions on whether this paper in fact strengthens the groups previous findings or whether it repeats the problems with the previous papers at a larger scale?
Have to wait for the paper to be out for the smarter forum members to scrutinise results

(To be clear, I mean smarter than me)
 
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