New research identifies faulty TRPM3 ion channel in ME/CFS immune cells

A faulty ion channel function is a consistent biological feature of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), providing long-awaited validation for hundreds of thousands of Australians living with the debilitating illness.

The new Griffith University research found a crucial cellular structure responsible for calcium transport, the TRPM3 ion channel, was faulty in immune cells from people with ME/CFS.

Director and senior author, Professor Sonya Marshall-Gradisnik from Griffith's National Centre for Neuroimmunology and Emerging Diseases (NCNED), said the TRPM3 played an essential role in calcium transport into cells, regulating responses properly in the body, immune function, and maintaining normal cellular balance.

When it fails, cells cannot function properly as calcium signalling is essential for healthy immune cell activity.

Our findings provide clear and definitive scientific evidence that TRPM3 ion channels are not working properly in people with ME/CFS."

Professor Sonya Marshall-Gradisnik from Griffith's National Centre for Neuroimmunology and Emerging Diseases (NCNED)

Using a gold-standard technique, the team confirmed a significant and reproducible reduction in TRPM3 activity in ME/CFS patients compared with healthy individuals, regardless of location, laboratory, or operator.

Professor Marshall-Gradisnik said reproducing results in another laboratory more than 4,000 kilometres apart showed just how robust this discovery was.

Lead author Dr Etianne Sasso said the discovery strengthened global scientific efforts to understand ME/CFS and validated the lived experiences of patients who had long struggled for recognition.

"These results provide further evidence for developing a diagnostic test for ME/CFS, and will also guide us toward new therapeutic targets, which could eventually lead to treatments which improve cellular function and overall quality of life for patients," she said.

Dr Sasso said people with ME/CFS had been facing stigma, disbelief and uncertainty, and the research showed their cells behaved differently in measurable ways.

"The faulty ion channels act like 'stuck doors', preventing cells from receiving the calcium they need," she said.

Dr Peter Smith, a clinician who treats ME/CFS patients, said the findings were an important step forward for medical practice.

"This research provides concrete biological evidence that supports what patients have been describing for decades," he said.

"Knowing there is a measurable cellular dysfunction helps us recognise ME/CFS as a legitimate medical condition and improves confidence in patient care.

"This breakthrough brings real hope for future treatment options."

ME/CFS symptoms included profound, persistent exhaustion; post-exertional malaise, pain, cognitive difficulties, dizziness, temperature instability and sensory sensitivity, severely restricting day-to-day functioning, education, employment and social participation.

The study was conducted across independent laboratory sites on the Gold Coast and in Perth, with participants recruited from South East Queensland, North East New South Wales, and Western Australia.

The study received funding support from the National Health and Medical Research Council of Australia and the Stafford Fox Medical Research Foundation.

Source:
Journal reference:

Sasso, E. M., et al. (2026). Large-scale investigation confirms TRPM3 ion channel dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Frontiers in Medicine. doi: 10.3389/fmed.2025.1703924. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1703924/full

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