Research Digest 30/04/21

Welcome to the 68th 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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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Where will the drugs come from?

Authors: Toogood PL, Clauw DJ, Phadke S, Hoffman D (Cayman Chemical Company USA)
Publication: Pharmacological Research
In this review the authors summarise recent research into the molecular basis of ME/CFS and progress being made towards the development of new tools for its diagnosis and treatment.
The authors review the evidence for several hypothesised aetiologies of ME/CFS, including infection, inflammation and immunity, and mitochondrial defects. They review progress towards a diagnostic biomarker, focussing on immune and metabolic disturbances.
Finally, they review treatment approaches, in particular noting that there are no approved pharmacological treatments for ME/CFS and that results of clinical trials have been disappointing. The authors provide an overview of current and new approaches to treatment in ME/CFS, including immunomodulators, antivirals, and medications targeting mitochondrial function. The authors also note that non-pharmacological treatments have limited evidence to support their efficacy and do not reverse the condition.
The authors note that the development of effective pharmacological treatments for ME/CFS has been hampered by many factors, including lack of diagnostic tools, heterogeneous samples and lack of awareness among health professionals, resulting in clinical trials which often are not of the highest standard. They conclude that, while interest from pharmaceutical companies has been non-existent to date, greater awareness of the condition could help attract the investment needed to develop effective treatments.

Antibody-dependent cell-mediated cytotoxicity (ADCC) in familial myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Authors: Sung AP, Tang JJ, Guglielmo MJ, Smith-Gagen J, Bateman L, Navarrete-Galvan L, Redelman DD, Hudig D (University of Nevada, USA)
Publication: Fatigue: Biomedicine, Health and Behavior
In a 1998 study, low natural killer (NK) lymphocyte activity was first identified as a risk factor for familial ME/CFS. Since then, many studies have examined NK cells in the context of the general ME/CFS population, but few have gone on to further understand the familial link. Antibody-dependent cell-mediated cytotoxicity (ADCC) is one way in which NK cells control viral infection. Given that there is growing literature to suggest viral aetiology for ME/CFS, this pilot study aimed to investigate NK-associated ADCC in familial ME/CFS.
Five families from which several members were diagnosed as having ME/CFS (Fukuda criteria) were enrolled into this study, this amounted to 11 ME/CFS and 22 healthy family members. 16 unrelated, age-, gender-, and race-matched healthy control patients were also recruited. Blood samples were collected from all patients and peripheral blood mononuclear cells (PBMCs) were extracted. Natural killer cells were isolated and quantified in terms of their abundance, activity capacity, and receptor variants.
CD16A is the NK cell receptor required for ADCC and as such the number of CD16A positive (CD16Apos) NK cells was quantified. The authors showed that CD16Apos NK cell counts and ADCC capacity were reduced in both the ME/CFS patients and their family members compared to the unrelated healthy controls. Furthermore, they show that within the ME/CFS families all members (both with or without ME/CFS) were more likely to have a combination of low ADCC activity with low CD16A NK cell counts than the unrelated controls, which could represent a familial synergistic risk for ME/CFS. Analysis of the FCGR3A gene (which encodes the CD16A receptor) proved to be inconclusive due to low patient numbers.
The authors conclude that their findings support a role for low ADCC as a risk factor for familial ME/CFS.

Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)

Authors: Lupo GFD, Rocchetti G, Lucini L, Lorusso L, Manara E, Bertelli M, Puglisi E, Capelli E (University of Pavia, Italy)
Publication: Scientific Reports
Recent studies have shown that there are strong correlations between dysbiosis (an imbalance of the gut microbial community) and the pathogenesis of both intestinal and extra-intestinal disorders. This study aimed to investigate the intestinal bacterial composition of ME/CFS patients as compared with healthy controls.
35 ME/CFS patients (diagnosed with the Fukuda criteria), 35 healthy relatives, and 35 healthy non-related control patients were recruited for this study. Faecal and salivary samples were obtained, DNA was extracted, and gut and oral microbiota were analysed.
It was revealed that there were significant variations in both the intestinal and oral bacteria between ME/CFS patients, their relatives, and external controls; with more marked differences observed in the gut. Interestingly, the authors note that the intestinal microbial profile of the ME/CFS patients was consistent with the profiles reported for other autoimmune conditions such as Crohn’s disease, Ulcerative Colitis, and Systemic Lupus Erythematous.
This study indeed confirmed dysbiosis in the intestinal microbiota of ME/CFS patients. The authors conclude that further, larger studies are required in order to better understand if the dysbiosis seen in ME/CFS patients are a cause or consequence of the onset of ME/CFS and if they are related to any of the several secondary symptoms.

Perceptions of European ME/CFS Experts Concerning Knowledge and Understanding of ME/CFS among Primary Care Physicians in Europe: A Report from the European ME/CFS Research Network (EUROMENE)

Authors: Cullinan J, Pheby DFH, Araja D, Berkis U, Brenna E, de Korwin JD, Gitto L, Hughes DA, Hunter RM, Trepel D, Wang-Steverding X (University of Warwick, UK)
Publication: Medicina
The European ME/CFS Research Network (EUROMENE) conducted a survey of its academic and clinical expert members to better understand the perceptions of GPs’ knowledge and understanding of ME/CFS.
23 EUROMENE members from 19 European countries completed the survey. Of these, 9 were academics, 8 were medical specialists and 8 were GPs. Some respondents held both academic and clinical roles.
65% of respondents indicated that there was no specific national guidance on treatment pathways for ME/CFS in their country. Some respondents noted that the clinical guidance in their country was either insufficient or still in development.
 The vast majority of respondents indicated that they believed that GPs lack confidence to recognise, diagnose and manage ME/CFS, and estimated that approximately 60% of people with ME/CFS are undiagnosed.
Respondents noted the impact of the widespread disbelief about the condition on the medical care offered to ME/CFS patients, especially the availability of specialist medical care, with many countries having little or no specialist care available. Where specialist care is available, psychiatric involvement was seen to be common.
All respondents agreed that there should be more ME/CFS content in undergraduate and postgraduate medical courses, and that short literature reference material should be available to medical practitioners. The importance for centres of excellence also emerged as a theme among respondents.

The Australian You+ME Registry is now open!
Emerge Australia is delighted to announce that the first Australian ME/CFS patient registry is now officially open! We have partnered with Solve M.E. in this landmark undertaking, which will help create the largest possible dataset and harness the power of big data to understand ME/CFS. The initiative is the first, critical step to the launch of the Mason Foundation-funded ME/CFS Biobank in Australia.
By signing up to the You+ME Registry, not only are you fuelling vital research into ME/CFS by sharing your unique health information, but you also gain access to the purpose built ME/CFS symptom-tracking app, as well as becoming eligible for blood sample donation to the Biobank.
Australian ME/CFS patients and healthy control volunteers can now sign up to participate in the Australian registry by clicking the link below.
Click here to join the You+ME Registry!
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