Full Summary of Projects
Project 1: Investigations into TRPM3 ion channel dysfunction in ME/CFS and Long COVID patients using electrophysiology
NCNED has previously and consistently reported impaired TRPM3 ion channel dysfunction in natural killer cells of ME/CFS patients, and more recently have published the same dysfunction in patients suffering Long COVID. This project continues to characterise TRPM3 ion channel dysfunction in the pathomechanism of disease, and as a potential target for diagnosis and treatment. This project utilises the gold-standard technique when investigation ion channel function, patch clamp electrophysiology.
Project 2: In vitro investigations into the potential therapeutic benefit of Naltrexone in restoring TRPM3 ion channel dysfunction in ME/CFS and Long COVID
There exists a crosstalk between TRPM3 ion channel function and Naltrexone biological activity. NCNED has previously reported in vitro treatment of natural killer cells have restored TRPM3 ion channel function in people with ME/CFS. This research project aims to elucidate the therapeutic benefit of naltrexone in ME/CFS and Long COVID through in vitro investigations using electrophysiology, immunofluorescence, and genotyping.
Project 3: Investigations into potential pharmacotherapeutic targets in ME/CFS and Long COVID
Currently, there is no evidence-based treatment for ME/CFS and Long COVID patients. While anecdotal data exists on the benefit of several medications, there is an absence of in vitro and clinical trial data. This project aims to elucidate the role of potential off-label treatment options through in vitro investigations using the immune or natural killer cell model and provide evidence for potential clinical trials.
Project 4: Investigations into the use of Low Dose Naltrexone in the treatment of Long COVID and ME/CFS: a randomised placebo-controlled clinical trial
NCNED have previously reported that ME/CFS patients taking Low Dose Naltrexone have restored TRPM3 ion channel function. This 12-week randomised placebo-controlled clinical trial aims to investigate clinical outcome measures in addition to potential benefit in immune and ion channel function in people with ME/CFS and Long COVID.
Project 5: Investigations into intracellular calcium signalling dysfunction and the potential role in mitochondrial dysfunction
There is substantial evidence that ME/CFS is an ion channelopathy condition, and few publications have reported impaired intracellular calcium signalling. Additionally, there exists strong evidence of mitochondrial dysfunction in the pathomechanism of illness. This project aims to elucidate the impact of calcium signalling dysfunction on mitochondrial function in the pathomechanism of ME/CFS and Long COVID using flow cytometry, electrophysiology, and super resolution confocal microscopy.
Project 6: Identification of TRPM3 ion channel isoforms as potential biomarker for ME/CFS
Further characterisation of TRPM3 ion channel dysfunction in ME/CFS and Long COVID requires elucidation of TRPM3 isoforms. The mammalian TRPM3 gene encodes for more than ten variants, some of which with differing pharmacological and functional capabilities. This project aims to use LC-MS to identify changes in TRPM3 isoforms in ME/CFS and Long COVID patients to determine their role in disease, diagnosis, and treatment.
Project 7: Further identification and validation of TRP ion channel single nucleotide polymorphisms in ME/CFS
NCNED previously reported on single nucleotide polymorphisms across different TRP family member genes in ME/CFS patients compared with healthy controls. This current project aims to validate previous findings in a large sample cohort and identify further genetic changes through genome-wide association studies using modern technology and recent knowledge.
Project 8: Health related quality of life in ME/CFS and Long COVID patients: a longitudinal investigation
Numerous publications have reported on the impaired quality of life of ME/CFS and Long COVID patients, however, there is an absence in longitudinal data across patient reported outcome measures employed. This investigation aims to report on health-related quality of life and impact of disease severity on ME/CFS and Long COVID patients during a study period of 12 months.
Project 9: Investigations into healthcare and health service satisfaction amongst people with ME/CFS and Long COVID
Many health consumers with ME/CFS and Long COVID report negative interactions or experiences with healthcare services when seeking diagnosis, treatment and/or care. Further, there is an absence of adequate diagnostic and treatment criteria when caring for a patient with ME/CFS and Long COVID. This project aims to validate reporting measures to determine patient experiences when seeking healthcare services in Australia.
Project 10: Investigations into the access of disability support services and measures of illness longevity to support NDIS applications
There is limited information on the economic impact of Long COVID in Australia. Preliminary data suggests that people suffering Long COVID have reported a 40% decrease in household income and are burdened by an increase in healthcare costs. This project aims to identify the economic burden (both direct and indirect) on Australians suffering Long COVID.
Project 11: Investigating regulatory dysfunction in ME/CFS and Long COVID using 7T MRI
Our research to date has detected abnormal autonomic control and impaired connectivity within the brainstem and default mode network. This project will apply functional MRI with improved SNR and spatial resolution to identify the nature and source of dysregulation within the brain of ME/CFS and Long COVID patients.
Project 12: Studying pathophysiology of ME/CFS and Long COVID patients using 7T and 3T MRI”
Preliminary results from our brain MRI research indicated microstructure changes in the brain of ME/CFS patients. This project will apply multimodal imaging techniques (QSM, myelin imaging, and diffusion) to detect tissue microstructural changes in the brain regions of ME/CFS and Long COVID patients.
Project 13: Investigating neurological changes in ME/CFS patients before and after Low Dose Naltrexone (LDN) using 7T and 3T MRI
ME/CFS patients have benefitted from Low Dose Naltrexone (LDN) therapy which has been reported to have a restorative effect in ME/CFS patients. This project will investigate neurological changes in ME/CFS and Long COVID patients before and after the LDN using multi-modal MRI techniques