By Professor Sonya Marshall-Gradisnik, Professor Don Staines, Dr Helene Cabanas and the NCNED Team, Griffith University, Queensland, Australia
Researchers from the National Centre for Neuroimmunology and Emerging Diseases (NCNED) at Griffith University in Queensland, Australia, have published more than 70 papers on ME and chronic fatigue syndrome. The NCNED host and present at international conferences and Prof Marshall-Gradisnik was on the Australian government’s advisory committee on ME and CFS, who delivered their report earlier this year.
NCNED co-directors Prof Sonya Marshall-Gradisnik and Prof Don Staines have worked in the field of chronic fatigue syndrome and Myalgic Encephalomyelitis for a decade. They are authors of the International Consensus Criteria for ME and Primer for Medical Practitioners. Read more about Prof Marshall-Gradisnik and Prof Staines in ‘Meet the Scientist’ interviews.
In this update, the NCNED explain their work, what they’ve found and the trials underway.
During the past four years, researchers at the NCNED have focused on a family of ion channels, known as Transient Receptor Potential (TRP) ion channels. These ion channels are located on nearly every cell type in the human body. Importantly, TRP ion channels play a crucial role in healthy cells – transferring calcium and other cations from outside the cell to the inside, resulting in regulation of many cell functions. Therefore, abnormal TRP ion channels lead to dysregulation of calcium signalling.
TRP channels are widely known to be involved in sensory reception, including thermoreception, chemoreception, mechanoreception, nociception /pain reception and photoreception and can be then related to many symptoms in many diseases including ME/CFS*.
Genetic variations in TRP ion channels have been previously reported by NCNED in immune cells from CFS/ME* patients.
Recently the NCNED has validated their previous research reporting an impaired function in a particular TRP ion channel, referred to as Transient Receptor Potential Melastatin 3 (TRPM3) ion channel, in immune cells from ME/CFS* patients.
What does this new data mean?
The NCNED team have now reported again that immune cells from a new cohort of ME/CFS* patients have faulty cell receptors compared with healthy participants. This results in reduced calcium being transported into the immune cell where cells are unable to function optimally causing immune system changes seen in ME/CFS* patients.
Given these receptors are located on nearly every cell type in the human body, their dysfunction will also affect other cells that have this receptor, for example, muscle, cardiovascular, gastrointestinal and neuroimmune cells are unable to effectively function. Consequently, this will lead to clinical presentation of ME/CFS* symptoms.
Specifically, in this recent study the NCNED team employed a gold standard technique called ‘patch clamp’ allowing the characterisation of TRPM3 function using two different drugs that have been well documented to activate TRPM3.
TRPM3 is activated by pregnenolone sulphate and nifedipine, that act on different parts of the receptor. The NCNED reported both drugs were unable to activate the TRPM3 to perform its function in ME/CFS patients compared with healthy controls.
Every ME/CFS* patient and healthy participant had more than six TRPM3 functional tests recorded for each drug. All ME/CFS* patients showed TRPM3 abnormality, and no abnormalities were found in healthy controls.
In summary these recent results from NCNED have identified TRP and TRPM3 dysfunction in the pathology of ME/CFS*. TRPM3 is not only confirmed in the pathology of ME/CFS but is now considered as a potential biomarker and targeted for future treatment for CFS/ME*.
Excitingly, NCNED is now testing other drugs to target TRP channels for benefitting ME/CFS* patients. These treatment-focused studies are currently underway.
*NCNED now use the 2003 Canadian Consensus Criteria and the 2011 International Consensus Criteria for ME. If the ME patients meet CCC and/or ICC they most certainly meet the Fukuda [criteria for chronic fatigue syndrome 1994] as it is very broad.
Read more: Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients, published in Molecular Medicine, April 2019.
The NCNED’s epidemiological study found 38% of Australians diagnosed with CFS and ME don’t meet the Fukuda chronic fatigue syndrome definition. More than two-thirds don’t meet the International Consensus Criteria for Myalgic Encephalomyelitis (ICC ME).