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Research Digest 30/06/22

Welcome to the 85th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles.

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As part of ME/CFS Awareness week last month, Emerge Australia hosted a research panel with four Australian ME/CFS researchers: Professor Paul Fisher (La Trobe University), Dr Sara Ballouz (Garvan Institute of Medical Research), Professor Ken Walder (Deakin University) and Dr Chris Armstrong (University of Melbourne). 
The panel presented on a range of topics, including mitochondrial function, sex differences, metabolomics, repurposing existing drugs for treatment, changes in eye movement, and the relationship between ME/CFS and Long COVID. In addition to hosting the event, Emerge Australia’s Research Manager, Dr Michelle Tavoletti, also provided an update on the Australian ME/CFS Biobank and Patient Registry. The event concluded with a Q&A with the panel responding to community questions.
This issue of our Research Digest provides a summary of the Research Panel. A recording of the entire event is available to view at the link below and video start times for each presentation have been included with each summary.

ME/CFS Research Panel

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Welcome

Host: Dr Michelle Tavoletti (Emerge Australia)
Video start time: 0 min
 
Emerge Australia’s Research Manager, Dr Michelle Tavoletti, opens the session, welcomes the panel and provides an update on Australia’s ME/CFS Biobank and Patient Registry.

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ME/CFS – Disease Mechanisms and Blood Tests

Presenter: Professor Paul Fisher (La Trobe University)
Video start time: 5 min 40 sec
 
In addition to chairing Emerge Australia’s Medical and Scientific Advisory Committee (MSAC), Prof. Fisher has contributed 40 years to the study of mitochondrial biology and cellular disfunction in neurodegenerative and neurological diseases/disorders, including ME/CFS. Paul’s laboratory has identified that mitochondrial activity in ME/CFS is altered, by demonstrating that: (i) ATP synthesis by Complex V is less efficient and (ii) the activity of the enzyme TORC1 is strikingly higher in ME/CFS compared to control cells.
 
In more recent studies evaluating protein expression and RNA transcription in ME/CFS lymphoblasts, Paul’s laboratory has identified a sizeable number of proteins and RNAs that are upregulated or downregulated in ME/CFS lymphoblasts, compared to control cells. In selecting the top 9 of either protein or RNA transcripts, Paul reported that these differences could confidently discriminate between ME/CFS and control cell lines, with a high degree of specificity and selectivity; attributes important for biomarker design.
 
Despite the promise of these studies, the routine use of lymphoblasts is not ideal for diagnostic use, given the time-consuming lymphoblast culture/growth process and the specialised expertise required for their culture. To improve the clinical potential of his findings, Paul’s lab isolated lymphocytes from blood cells, proving to be a more efficient and diagnostic lab-friendly process. By measuring RNA expression of 9 transcripts identified to discriminate ME/CFS from control cells by PCR (like the method employed for Covid-19 diagnosis), Paul’s laboratory has developed a much more robust and efficient method for the diagnosis of ME/CFS, with demonstrated diagnostic potential of 100% specificity and 95% selectivity. Providing adequate funding can be secured, Paul hopes that this remarkably simple PCR test could be upscaled and ready for clinical trial in approximately 12 months’ time.

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Exploring the Sex Differences in ME/CFS through Integrated Computational Analyses

Presenter: Dr Sara Ballouz (Garvan Institute of Medical Research)
Video start time: 24 min 24 sec
 
Dr. Ballouz is a bioinformatics and functional genomics researcher with interests in understanding the genetic factors in diseases which are attributable to sex differences. With knowledge that ME/CFS is highly sex-biased, Sara’s research aims to explore why this sex bias exists and how it arises in ME/CFS.
 
Sara’s presentation highlighted that there are (i) two peaks of age onset for women with ME/CFS, corresponding to hormonal changes observed during puberty and menopause and (ii) that male and female immune systems differ and change with age. By implementing single cell genomics to study one cell at a time, Sara’s research seeks to understand what role hormones and the immune system have on sex differences in ME/CFS. Utilising blood cells, Sara will assess the cell’s DNA and the immune function from both sexes at different ages, comparing the cells of those with ME/CFS to those of healthy controls.
 
Sara is also making use of ME/CFS Patient Registry data from both Australia and the US to design a computer/software algorithm to study ME/CFS. By studying triggers, symptoms and other patient experiences, Sara hopes that the newly generated algorithm will be able to distinguish different ME/CFS types that may later help predict who may be more susceptible to ME/CFS across different populations.

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Overview of NHMRC-Funded CHROMIC Project

Presenter: Professor Ken Walder (Deakin University)
Video start time: 36 min 10 sec
 
Prof. Walder is Chair of Metabolic Diseases at Deakin University’s School of Medicine, and leads the ME/CFS Chromic Study. His ME/CFS research aims to better understand the underlying pathophysiology of ME/CFS and to discover new treatment options for ME/CFS, using off-patent drugs.
 
Off-patent drugs are medications that have been safely used in the past for patients with different diseases but whose patents have now expired. These drugs have already been through clinical trials for other conditions, which means that if an off-patent drug is identified that could be potentially useful for treating ME/CFS, the clinical trial process will be much quicker than it would be for new drugs, as the safety tests and doses have already been conducted and determined for these drugs.
 
For his Chromic study, Ken plans to recruit 100 participants (50 ME/CFS patients and 50 healthy controls). Blood donated by these patients will be utilised to isolate blood cells that will be cultured under specific conditions to form muscle (skeletal) and brain (cortical) cells. These two cell models have been chosen as muscle and brain cells are the largest consumers of energy in the body.
 
These simplified cell models will be utilised to mimic what may be occurring in the human bodies of people with ME/CFS compared to healthy controls; in particular, to better understand how mitochondrial function is impacted in ME/CFS. The DNA in these cell models will also be analysed to identify genes that best differentiate ME/CFS from control cell lines, and these will then be used to determine the potential of off-patent drugs to treat ME/CFS, helping to identify potential new treatments.

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Melbourne ME/CFS Research Collaboration

Presenter: Dr Chris Armstrong (University of Melbourne)
Video start time: 48 min 0 sec
 
Dr Armstrong is the Director of the Melbourne ME/CFS Collaboration, one of Open Medicine Foundation’s global research hubs. Chris collaborates with both Australian and international researchers and is also a valued member of Emerge Australia’s Medical and Scientific Advisory Committee  (MSAC).
 
Chris is working on several projects, with a working model of ME/CFS as a disease comprising many different pathways which lead towards a common biology, resulting in the observed disease expression and altered function. 
 
In collaboration with researchers at Stanford University in the US, patients with ME/CFS, Long Covid and Lyme disease are studied to assess the similarities and differences in protein expression following a flare up event, with blood sampling, heart rate monitoring and symptom evaluation conducted at multiple time points. In Sweden and in collaboration with Uppsala University, patients with Long Covid and Herpes Simplex virus are studied to determine which of these patients progress to develop ME/CFS.
 
Locally, Chris’ research interests include a sex hormone study, based on the prevalence of ME/CFS in women and studying the changes to menstrual hormone levels and how this correlates to post-exertional malaise (PEM). Home testing of blood, urine, and heart rate monitoring (via smart watches) are employed to uncover how hormones might be exacerbating ME/CFS symptoms, pre- and post-PEM.
 
Chris is also collaborating with Monash University to investigate eye movement in patients living ME/CFS. The Ocular Motor Study aims to: (i) develop a diagnostic test for neurologists to perform, (ii) produce an objective measure of fatigue that can be used in ME/CFS treatment trials and (iii) characterise PEM induced by cognitive exertion. The outcome of the Ocular studies will also be complemented by analysis of metabolomics from blood and urine samples.

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Panel Q&A

Host: Dr Michelle Tavoletti (Emerge Australia)
Video start time: 1 hr 4 min
 
The panel responds to questions from the ME/CFS patient community.

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