Research we fund / support
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Below are summaries of research we funded prior to 2016, when we launched our five-year strategy with a focus on funding PhDs and our Clare Francis Fellowship.


Understanding muscle dysfunction

The funding provided by Action for M.E. was matched by Newcastle University’s Faculty of Medical Sciences to establish the Action for M.E. PhD Studentship. Top science graduate Gina Rutherford was trained and employed to work on this study over three years.

The study aimed to establish in vitro approaches to exploring the inter-relationship between muscle function, acidosis and fatigue expression with a view to developing treatments to be used in subsequent clinical trials.

  • Led by: Dr Phil Manning and Prof Julia Newton at Newcastle University.
  • Cost: £25,000
  • Study began: May 2012

Project summary by Gina Rutherford, Newcastle University

M.E. is a debilitating disorder of unknown aetiology and is characterised by severe disabling fatigue in the absence of an alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue. However, this model is at odds with patient descriptions of their fatigue, with many citing difficulty in maintaining muscle activity due to perceived lack of energy and discomfort.

Studies have demonstrated that when M.E. patients complete relatively low-level repeat exercise, they experience profound muscle dysfunction which is accompanied by acidity in the muscle. This has been speculated to be due to abnormalities within the muscle.[1],[2]

These abnormalities may lead to patients using anaerobic energy-producing pathways, rather than aerobic energy pathways that enable the muscle to function for longer without excessive fatigue. Studies that have reported abnormality have used magnetic resonance spectroscopy (MRS) to measure internal pH of the lower limb musculature in patients.

In this project, muscle samples were obtained from M.E. patients in an attempt to investigate muscle function in more detail. This involved using novel approaches to measure pH at rest and following electrical impulse stimulation which functioned to experimentally mimic muscular contraction and simulate exercise. Furthermore, other approaches were used to investigate specific energy producing pathways such as glycolysis (anaerobic respiration) and mitochondrial oxidative phosphorylation (aerobic respiration).

During each experiment, the cells were treated with key drug compounds to test the capacity of new drugs to modulate cellular energy production and to investigate the capacity of these drugs to treat peripheral muscle fatigue in M.E.

Fluorescent dye was used to measure the pH inside the muscle. Interestingly, there was no difference in pH when M.E. muscle samples were compared to healthy control sample, which contrasts previous work conducted when M.E. patients performed an exercise intervention .

When specifically measuring glycolytic (anaerobic) activity there was no significant difference in lactate which is produced at a rate comparable to glycolysis or any of the glycolytic parameters measured.

Mitochondrial (aerobic) function was also assessed using a technique called extracellular flux analysis, which measures the rate of cellular oxygen consumption. Data revealed there to be no differences in the mitochondrial function of M.E. muscle cells compared to healthy control samples. Thus, it can be determined that mitochondrial dysfunction is not the cause of muscle fatigue symptomology experienced by M.E. patients.

Free radical generation in M.E. muscle samples was also investigated in this project. Briefly, free radicals are atoms that contain an unpaired electron in their outermost ring, this results in a highly reactive configuration which will readily interact with other molecules to become stabilised, which is potentially damaging to key components of the cell and could lead to cellular dysfunction.

However, the results demonstrated there to be no evidence of elevated free radical generation when compared to control samples. This would suggest that the muscle fatigue phenotype exhibited in M.E. patients is not related to elevated oxidative stress at the isolated muscle cell level.

This research project did not find any evidence of biochemical or metabolic dysfunction in muscle cell samples obtained from CFS/M.E. patients. This contrasts previous work that has reported muscle dysfunction in CFS/M.E. patients following exercise. Further investigations are required to determine the biological basis of fatigue in M.E. patients.

[1] Jones DJ, Hollingsworth KG, Jakovijevic DG, Fattahova G, Pairman J, Blamire AM, Trennel MI and Newton JL (2012) Loss of capacity to recover from acidosis on repeat exercise in CFS/M.E. patients-a case control study. European Journal of Clinical Investigation. 42(92):186-194

[2] Jones DJ, Hollingsworth KG, Taylor R, Blamire AM and Newton JL (2010) Abnormalities in pH handling by peripheral muscle and potential regulation of the autonomic nervous system in chronic fatigue syndrome. Journal of Internal Medicine. 267(4):394-401


Neurophysiology of pain in M.E.

Action for M.E. took over the management of this study in July 2014, following the closure of the CFS Research Foundation, which had already secured and allocated funding for it.

  • Duration of study: January 2014 to October 2017
  • Led by: Prof Peter White and Dr Julius Bourke
  • Aims: To discover the physiological and chemical abnormalities underlying pain experienced by people with M.E.

In his report to Action for M.E.'s Research Panel, Dr Julius Bourke says:

"This is the first study, to the authors’ knowledge, that has provided clear and validated evidence of the presence of central sensitisation in both CFS and fibromyalgia. It is also the first study to compare fibromyalgia and chronic fatigue syndrome in this regard [...] The clinical relevance of central sensitisation in CFS and fibromyalgia is twofold – firstly in that QST are essentially bedside tests and can be performed in the clinic; the second is that it may have potential as a therapeutic drug target, defining a physiological abnormality that may be moderated by pharmacological correction.


Immune responses in M.E.

Project summary by Prof Stephen Todryk, Northumbria University

There are likely to be many causes of M.E., but various laboratories report that immune function in people with M.E. is different to otherwise healthy people. M.E. often follows after an infection, and the immune response that usually fights the infection may become out of control in M.E. So the measurement of immune responses may tell us about the cause and severity of a person’s disease and suggest how it can be treated.

Our research in Newcastle has involved the clinical network at the local hospitals and the immunology lab at Northumbria University. We recruited 50 people with M.E. whose illness was measured for severity, and we made many measurements of their immune systems (white blood cells and antibodies).

We found that people with worse disease had fewer cells called natural killer (NK) cells, known to fight viruses. They also had less antibody against bacteria called mycoplasma, but more inflammatory interferon. This is interesting, and the study of larger numbers of patients over a period of time will help to prove these associations, making these measurements useful for working out new and effective ways of diagnosis and treatment of M.E.

Significant results:

  • NK cells are reduced with increased fatigue severity
  • CD57+ NK cells are reduced with increased fatigue severity
  • Antibodies against Mycoplasma are reduced with increased fatigue severity
  • Non-specific IFN-gamma production is increased with increased fatigue severity
  • CMV IgM is increased with increased fatigue severity