Neuroimaging and Ion Channel Research
1 NCNED TRPM3 Ion Channel Programme
Principal Investigator:: Sonya Marshall-Gradisnik, Professor of Immunology
Institution:: National Centre for Neuroimmunology and Emerging Diseases (NCNED), Griffith University, Australia
Contact/URL:: https://www.griffith.edu.au/research/health/national-centre-neuroimmunology-emerging-diseases
Funder:: Institutional and NHMRC (Australia)
Status:: Active (multiple ongoing studies)
Phase:: Observational and interventional (LDN trials planned)
Cohort:: ME/CFS and Long Covid patients (multiple cohorts)
Mechanism/Focus:: Systematic investigation of TRPM3 ion channel dysfunction in ME/CFS. January 2026 publication confirmed consistent TRPM3 malfunction using gold-standard patch-clamp techniques. Also conducting 7T MRI studies revealing hippocampal volume alterations. Preparing LDN clinical trials for both ME/CFS and Long Covid.
Primary Outcomes:: TRPM3 channel function; hippocampal volume changes; LDN trial endpoints TBD
Estimated Completion:: Ongoing programme (multiple studies)
Timeline:: TRPM3 confirmation published January 2026; 7T MRI study published February 2025; LDN trials in preparation; $438,000 grant for longitudinal brain imaging (progression study)
Publication Medium:: Published in PLOS ONE and specialty journals; future publications expected similarly
Document Relevance:: Ch. 8 (neurological dysfunction), Ch. 7 (immune dysfunction—ion channels), Ch. 20 (biomarker research)
The NCNED programme is distinctive for its sustained, systematic focus on a single molecular target (TRPM3) across multiple methodologies. The January 2026 patch-clamp confirmation elevates TRPM3 dysfunction from an association to a consistently reproducible cellular phenotype—a rare achievement in ME/CFS research. The planned LDN trials will test whether modulating neuroinflammation (a proposed upstream driver of ion channel dysfunction) improves TRPM3 function and clinical outcomes, creating a mechanistic link between treatment and pathophysiology. The 7T MRI hippocampal findings add a neuroanatomical dimension that connects to cognitive complaints reported by patients.
2 Charit'{e Neuroimaging Biomarker Study}
Principal Investigator:: Carmen Scheibenbogen, MD (PI); neuroimaging team at Charité
Institution:: Charité – Universitätsmedizin Berlin, Germany
Contact/URL:: https://mecfs-research.org/en/researchfunding-charite-biomarker2/
Funder:: ME/CFS Research Foundation (Germany)
Status:: Funded; starting January 2026
Phase:: Observational (neuroimaging biomarker development)
Cohort:: ME/CFS patients undergoing immunoadsorption treatment
Mechanism/Focus:: Investigates whether functional brain changes— particularly thalamocortical hyperconnectivity—can be modulated by immunoadsorption. Tests whether CNS abnormalities normalise after peripheral autoantibody removal, linking the autoimmune and neurological hypotheses.
Primary Outcomes:: Pre/post-treatment fMRI connectivity changes; correlation with clinical improvement and autoantibody levels
Estimated Completion:: Not yet announced (recently funded)
Timeline:: Funding confirmed late 2025; project starting January 2026
Publication Medium:: Not yet announced
Document Relevance:: Ch. 8 (neurological dysfunction), Ch. 7 (immune dysfunction—autoantibodies), Ch. 13 (integrative models)
This study bridges two major ME/CFS hypotheses: autoimmunity and central nervous system dysfunction. By imaging the brain before and after immunoadsorption, it can test whether peripheral autoantibody removal reverses central connectivity abnormalities—a question that goes beyond symptom improvement to mechanistic understanding. If thalamocortical hyperconnectivity normalises with autoantibody reduction, it would provide the strongest evidence yet that peripheral immune dysregulation drives CNS pathology in ME/CFS rather than the reverse.
3 Hyperbaric Oxygen Therapy for ME/CFS
Principal Investigator:: Multiple PIs
Institution:: Multi-site (USA / Germany)
Contact/URL:: https://doi.org/10.1101/2025.10.29.25339096
Registry ID:: NCT06118138 (post-COVID/ME/CFS HBOT study)
Funder:: ME/CFS Research Foundation / institutional
Status:: Pilot results published (preprint October 2025); larger RCT in planning
Phase:: Phase 1–2 (open-label pilot)
Cohort:: \(n=30\) ME/CFS patients, 40 HBOT sessions each
Mechanism/Focus:: Hyperbaric oxygen therapy (2.4 ATA, 100% O2) to address tissue hypoxia, neuroinflammation, and endothelial dysfunction. Pre- and post-treatment fMRI assessed thalamic connectivity.
Primary Outcomes:: SF-36 physical functioning significantly improved. Exercise capacity, muscle strength, and information processing speed all improved. Thalamic hyperconnectivity normalised post-HBOT
Estimated Completion:: Pilot published; RCT timeline TBD
Publication Medium:: medRxiv preprint; peer review pending
Document Relevance:: Ch. 8 (neurological dysfunction), Ch. 10 (cardiovascular), Ch. 19 (integrative approaches)
The normalisation of thalamic hyperconnectivity after HBOT provides the most direct interventional evidence to date linking brain connectivity abnormalities to a treatable target in ME/CFS (2025). However, the open-label design and small sample size preclude definitive conclusions; placebo effects are substantial for fatigue interventions, and a sham-controlled design (e.g., 1.3 ATA room air) is essential. The overlap with brainstem hypoperfusion research strengthens the rationale for oxygen-targeting approaches.