Does muscle bioenergetic abnormality cause peripheral fatigue in ME/CFS?


Senior Member
Does muscle bioenergetic abnormality cause peripheral fatigue in ME/CFS?
Prof. David Jones and colleagues

Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, UK

Background and aims
In the historical literature, the hallmark of myalgic encephalomyelitis (ME) was marked muscle fatigability often in response to minor degrees of exercise. Muscle cramps, fasciculations (twitching) and extreme muscle tenderness were also common findings. As Dr Ramsay said in the Postgraduate Medical Journal in 1978, “This was sometimes obvious as the patients winced even on light palpitation of the affected muscle; but much more frequently it took the form of minute foci of muscle tenderness which had to be carefully sought and for no ostensible reason were generally found in the trapezii and gastrocnemii.”

Today, patients diagnosed with ME/CFS frequently highlight the importance of peripheral fatigue — such as impairment of muscle power — in their experience of illness. Research in other chronic diseases, including published work by Prof. Jones at the Institute of Cellular Medicine on the autoimmune liver disease primary biliary cirrhosis, has highlighted important downstream biological mechanisms that appear to underpin fatigue. A number of these processes are, intriguingly, common to many chronic diseases, including ME/CFS; previous work has highlighted the frequency with which dysfunction of the autonomic nervous system is seen in both ME/CFS and primary biliary cirrhosis patients, as well as patients with many other conditions. The potential for shared mechanisms behind the expression of fatigue (if not its pathogenesis) is suggested by other recent work in the Institute of Cellular Medicine highlighting the close similarities in the phenotype of fatigue seen in a number of chronic diseases and ME/CFS.

In novel studies at the University of Newcastle using magnetic resonance scanning of peripheral muscle in ME/CFS patients (a scanning technique which looks at the way in which muscle is working), significant abnormalities in the handling of acid within muscle during exercise have been observed. It might be that acid build-up during exercise in ME/CFS patients results from reduced function of an important energy-generating enzyme within the mitochondria (the “batteries of the cell”) causing peripheral fatigue which “feeds-back” to the brain.

Given these findings, the aim of this project is to study, in the in vitro setting, the function of an energy-generating enzyme which the researchers hypothesise might be under-functioning in ME/CFS. A range of in vitro studies will be undertaken, all based on primary assay and culture of muscle cells (myocytes) derived from ME/CFS patients (fulfilling the Canadian criteria for ME/CFS) and matched normal and chronic disease controls (following establishment of the techniques using existing myocyte cell lines).

There are two broad aspects to the proposed investigative strategy. In the first (already funded by the Northern Clinical Network in Newcastle), an examination will be made of the function of ME/CFS patients’ muscle cells which have been grown in culture; the muscle biopsies taken during this phase represent a unique opportunity to study the pathways of metabolism within muscle, exploring the expression of the key energy generating enzymes and the cell proteins which help to control acid build up within the cell. The second aspect (funded by ME Research UK) involves array studies to look at metabolic gene expression in muscle. It is hoped that the results will show whether gene expression is altered in cultured muscle cells from patients with ME/CFS, and whether the change in gene expression with exercise in vitro is impaired in these muscle cultures.

This interesting range of studies builds on existing academic strengths in muscle energetics and culture, together with nanotechnology development, all of which are applied to the illness ME/CFS for the first time.

-->> trapezii
Main Entry: trapezius
Pronunciation: \-zē-əs\
Function: noun
Inflected Form(s): plural -zii \-zē-ˌī\ also trapeziuses
Etymology: New Latin, from trapezium; from the pair on the back forming together the figure of a trapezium
Date: circa 1704
: a large flat triangular superficial muscle of each side of the upper back