Summary: Researchers have identified a promising approach to treat long COVID by restoring ion channel function in immune cells using low-dose naltrexone. Published in Frontiers in Immunology and led by Griffith University’s National Centre for Neuroimmunology and Emerging Diseases (NCNED), the finding mirrors earlier work in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and suggests a shared biological mechanism between the two conditions.
This discovery offers hope for reducing symptoms such as brain fog, persistent fatigue, and other systemic problems that affect daily life. With clinical trials planned for both long COVID and ME/CFS, researchers will test whether repurposing low-dose naltrexone can provide meaningful relief.
Key Facts:
- Ion Channel Restoration: The research targets TRPM3 ion channel dysfunction in immune cells, restoring their ability to regulate ion flow and cellular signaling—processes linked to symptoms experienced by patients.
- Repurposing Naltrexone: Naltrexone, a medication with established clinical use, has shown the ability in laboratory experiments to restore TRPM3 channel activity and normalize calcium handling in immune cells.
- Planned Clinical Trials: Griffith University’s NCNED will run two clinical trials to evaluate the effectiveness of low-dose naltrexone in people with long COVID and those with ME/CFS.
Source: Griffith University
Overview of the discovery
Researchers at Griffith University’s National Centre for Neuroimmunology and Emerging Diseases (NCNED) report a world-first laboratory finding: they restored faulty ion channel activity on immune cells taken from people with long COVID using naltrexone. The work builds on prior NCNED research showing similar TRPM3 ion channel dysfunction in patients with ME/CFS, pointing to a potential shared pathophysiology.
PhD candidate Etianne Sasso, first author on the study, explains that ion channels are membrane proteins that control the movement of charged particles such as calcium into and out of cells. Proper ion flow is essential for immune cell function and for many biological processes across the body.
By restoring TRPM3 channel activity, the team observed normalization of calcium influx in immune cells, which could underlie improvements in symptoms such as cognitive dysfunction, debilitating fatigue, and disturbances to cardiovascular and gastrointestinal function reported by patients.
Professor Sonya Marshall-Gradisnik, senior author and Director of NCNED, emphasized that electrophysiology—the gold standard for measuring ion channel activity—confirmed the findings and strengthens the rationale for moving toward clinical testing.
The NCNED plans two clinical trials: one focused on people living with long COVID and a second trial enrolling patients with ME/CFS. Both will evaluate the safety and efficacy of low-dose naltrexone as a potential therapeutic option aimed at restoring TRPM3 channel function and improving patient outcomes.
If the trials demonstrate clinical benefit, low-dose naltrexone could become an accessible, repurposed treatment option that meaningfully improves quality of life for people affected by long COVID and ME/CFS.
About this neuropharmacology and long-COVID research
Author: Etianne Sasso
Source: Griffith University
Contact: Etianne Sasso, Griffith University
Image credit: Neuroscience News
Original Research (open access): “Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target” by Etianne Sasso et al., published in Frontiers in Immunology. The study examines TRPM3 dysfunction in post-COVID-19 condition (long COVID) and explores naltrexone’s effects on restoring ion channel activity in vitro.
Abstract
Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target
Introduction:
Previous work identified Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction in natural killer (NK) cells from people with ME/CFS. Recognizing similar symptoms and potential overlapping mechanisms, the authors investigated whether TRPM3 dysfunction also occurs in post-COVID-19 condition (long COVID). With no universally effective treatment for long COVID, insights from ME/CFS research may guide therapeutic development.
Naltrexone hydrochloride (NTX) has been reported as a beneficial pharmacological intervention in ME/CFS, and experimental studies indicated NTX can restore TRPM3 function in NK cells. The study aimed to: (i) validate impaired TRPM3 function in post-COVID-19 condition patients compared with ME/CFS and healthy controls; and (ii) evaluate NTX effects on TRPM3 activity in cells from post-COVID-19 condition patients.
Methods:
Whole-cell patch-clamp electrophysiology characterized TRPM3 activity in freshly isolated NK cells from participants with post-COVID-19 condition (N = 9; mean age 40.56 ± 11.26 years), ME/CFS (N = 9; mean age 39.33 ± 9.80 years), and healthy controls (HC; N = 9; mean age 45.22 ± 9.67 years). To test NTX effects, NK cells from post-COVID-19 condition participants (N = 9) and HC (N = 7) were incubated for 24 hours under two protocols: treated with 200 µM NTX or left untreated, after which TRPM3 function was assessed by patch-clamp recording.
Results:
The study confirmed impaired TRPM3 channel activity in NK cells from both post-COVID-19 condition and ME/CFS patients compared with healthy controls. Crucially, Pregnenolone sulfate (PregS)-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post-COVID-19 condition participants. After NTX treatment, the sensitivity of NK cells to ononetin did not differ significantly between post-COVID-19 condition and healthy controls.
Discussion:
These findings reinforce a shared pattern of TRPM3 ion channel dysfunction in ME/CFS and post-COVID-19 condition and demonstrate, for the first time, that in vitro NTX treatment can restore TRPM3 activity in NK cells from long COVID patients. Restoring TRPM3 function may re-establish TRPM3-dependent calcium influx, which is integral to proper immune cell signaling and broader physiological regulation. The results support NTX as a candidate therapeutic intervention and propose TRPM3 channel activity as a potential biomarker and treatment target for post-COVID-19 condition.