The ME Association End of Week Research Round-up and Index Update | 01 May 2020


Charlotte Stephens, Research Correspondent, ME Association.

We show below brief summaries of the research studies about ME/CFS that have been published in the last week, followed by the abstracts from those studies.

This information has been included in the monthly update to the central Research Index which is freely available as a download.

The Index has now been updated to include all studies up to the 30th April 2020.

This is an A-Z index of the most important published research studies and selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS).

You can also find the Research Index in the Research section of the website together with a list of Research Summaries from the ME Association that provide lay explanations of the more important and interesting work that has been published to date.

ME/CFS Research Published 24th – 30th April 2020

This week, 3 new research studies have been published:

1. A study from researchers in California and Germany, with Dr Robert Naviaux as the co-senior author, finding possible HHV-6 reactivation in some people with ME/CFS, leading to structural changes in mitochondria which provide a level of protection against some viruses, but at the cost of drastically decreased cellular energy production. We will be producing a summary review on this study shortly.

2. Australian researchers explored patients experiences of a five-week aquatic exercise programme. They found that self-paced group aquatic exercise is a safe, enjoyable and effective mode of exercise rehabilitation for people with ME/CFS, with psychosocial benefits.

3. A review of metabolomics research (studying changes in metabolites that could serve as biomarkers of disease) in ‘central sensitivity syndromes’, including metabolomics research in ME/CFS.

ME/CFS Research References and Abstracts

1. Schreiner P et al. (2020)
Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
ImmunoHorizons 4 (4): 201-215.

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disorder with many possible triggers. Human herpesvirus (HHV)–6 and HHV-7 are two infectious triggers for which evidence has been growing.

To understand possible causative role of HHV-6 in ME/CFS, metabolic and antiviral phenotypes of U2-OS cells were studied with and without chromosomally integrated HHV-6 and with or without virus reactivation using the histone deacetylase inhibitor trichostatin-A.

Proteomic analysis was conducted by pulsed stable isotope labeling by amino acids in cell culture analysis. Antiviral properties that were induced by HHV-6 transactivation were studied in virus-naive A549 cells challenged by infection with influenza-A (H1N1) or HSV-1.

Mitochondria were fragmented and 1-carbon metabolism, dUTPase, and thymidylate synthase were strongly induced by HHV-6 reactivation, whereas superoxide dismutase 2 and proteins required for mitochondrial oxidation of fatty acid, amino acid, and glucose metabolism, including pyruvate dehydrogenase, were strongly inhibited.

Adoptive transfer of U2-OS cell supernatants after reactivation of HHV-6A led to an antiviral state in A549 cells that prevented superinfection with influenza-A and HSV-1. Adoptive transfer of serum from 10 patients with ME/CFS produced a similar fragmentation of mitochondria and the associated antiviral state in the A549 cell assay.

In conclusion, HHV-6 reactivation in ME/CFS patients activates a multisystem, proinflammatory, cell danger response that protects against certain RNA and DNA virus infections but comes at the cost of mitochondrial fragmentation and severely compromised energy metabolism.

2. Broadbent S et al. (2020)
Patient experiences and the psychosocial benefits of group aquatic exercise to reduce symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a pilot study.
Fatigue: Biomedicine, Health and Behaviour [Epub ahead of print].

Abstract
Background: The aim of the study was to explore the experiences of participants in a short aquatic exercise programme for individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and to gain insight into the perceived psychosocial benefits. 

Methods: The exercise programme was of five-weeks duration, with two self-paced aquatic sessions per week. Eleven female participants (mean age 54.8 ± 12.4 yr) reported the onset and changes (24–48 h) in post-exercise fatigue, pain and other symptoms after each session, and completed a post-intervention interview comprising nine open-ended questions, with additional discussions. The reported symptoms and interview responses were entered into a spreadsheet, grouped and coded to identify the themes and subthemes. 

Results: The main themes were ‘symptoms’, ‘benefits’, ‘engagement and compliance’, and ‘limitations’. The analysis found that group aquatic exercises reduced social isolation through shared experiences and enhanced support; were beneficial and enjoyable without exacerbating symptoms; were preferable to other modes of exercise; and were seen as a long-term exercise option. Participants reported a reduction in pain, fatigue and anxiety after the intervention. 

Conclusions: Psychosocial benefits suggest that self-paced group aquatic exercise is a safe, enjoyable and effective mode of exercise rehabilitation for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

3. Miller J et al. (2020)
Metabolomics in Central Sensitivity Syndromes.
Metabolites 10 (4): 164.

Abstract
Central sensitization syndromes are a collection of frequently painful disorders that contribute to decreased quality of life and increased risk of opiate abuse. Although these disorders cause significant morbidity, they frequently lack reliable diagnostic tests.

As such, technologies that can identify key moieties in central sensitization disorders may contribute to the identification of novel therapeutic targets and more precise treatment options. The analysis of small molecules in biological samples through metabolomics has improved greatly and may be the technology needed to identify key moieties in difficult to diagnose diseases.

In this review, we discuss the current state of metabolomics as it relates to central sensitization disorders. From initial literature review until Feb 2020, PubMed, Embase, and Scopus were searched for applicable studies. We included cohort studies, case series, and interventional studies of both adults and children affected by central sensitivity syndromes.

The majority of metabolomic studies addressing a CSS found significantly altered metabolites that allowed for differentiation of CSS patients from healthy controls. Therefore, the published literature overwhelmingly supports the use of metabolomics in CSS. Further research into these altered metabolites and their respective metabolic pathways may provide more reliable and effective therapeutics for these syndromes.

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