New award from the MEA Ramsay Research Fund for further mitochondrial research | 21 July 2015

ME ASSOCIATION RAMSAY RESEARCH FUND:RESEARCH FUNDING ANNOUNCEMENT

Comparison of results from a commercial and a clinical diagnostic-based blood test to assess mitochondrial function in ME/CFS

The MEA Ramsay Research Fund is pleased to announce an award of £21,305 to Dr Sarah Jayne Boulton and colleagues at Newcastle University.

The award will be funding a new research study that will be comparing the results of a commercial blood test for mitochondrial function that has been developed by Dr Sarah Myhill and colleagues with the results from an international and widely accepted test of mitochondrial function which has a long and successful track record in clinical diagnosis and research of muscle disease, particularly in the UK.

BACKGROUND

Mitochondria play a vital role in energy production at a cellular level, especially in skeletal muscle, and a number of research studies – including some carried out at Newcastle University – have demonstrated abnormalities in muscle in people with ME/CFS that are linked to mitochondrial function.

The ME Association therefore believes that research into mitochondrial dysfunction in ME/CFS should be a high priority research item – as does the Medical Research Council.

This is why we have already funded a study that was carried out by Professor Julia Newton and colleagues at Newcastle University and we are currently funding, along with the Medical Research Council, further research into mitochondrial dysfunction. This is being carried out by Professor Anne McArdle and colleagues at the University of Liverpool.

We have also made a contribution to research that is being carried out by Dr Joanna Elson at Newcastle University, which is looking at mitochondrial DNA.

DIAGNOSIS OF MITOCHONDRIAL DYSFUNCTION

Interest in the role of mitochondrial dysfunction in ME/CFS has also led to the development of a commercial blood test – often referred to as the ATP profiling test – by Dr Sarah Myhill and colleagues (references 1 and 2).

In very simple terms, the test measures a number of components that determine a person’s ability to generate a substance called ATP, which is the cell’s unit of energy currency at a molecular level.

However, this test has not been validated by independent assessments. It is not therefore used to diagnose mitochondrial disease in the NHS.

The comparison study involves using a series of spectroscopic assays which are based upon published assays both for research and diagnosing mitochondrial disease, and the functionality of individual mitochondrial respiratory complexes are determined. These assays have been validated by other independent groups and laboratories.

These respiratory chain complexes, like links in a chain, must all be fully functional and tightly cooperative to allow the necessary ATP-producing oxidative phosphorylation reactions to occur. Any ‘weak link’ in the respiratory chain will result in sub-optimal respiratory function, poor ATP production and metabolic dysfunction, of which fatigue is a major symptom.

An array of spectroscopic mitochondrial diagnostic techniques to measure the respiratory chain complexes were first reported by Newcastle University in 1994 (reference 3) and were the foundation for current clinical diagnostic assays in the UK.

And in October 2014, Dr Boulton began a six month project funded by the MRC Confidence in Concept call that investigates the usefulness of the spectroscopic methods in stratifying ME/CFS patients based on their mitochondrial respiratory complex function.

Pilot data that supported the hypothesis of mitochondrial respiratory Complex II involvement in fatigue was generated from cultured muscle.

HOW WILL THIS COMPARISON OF TESTS WILL BE CARRIED OUT?

The research will involve a comparison between the data generated using the ATP profiling tests and the established mitochondrial complex assays using spectrophotometric techniques.

The aim is to determine the efficacy of each set of tests in relation to ME/CFS. In the exciting case that a synergy between the two diagnostic approaches exists, it is hoped that this preliminary study will promote an investigation into a more inclusive and highly resolved analytical technique for metabolic testing of people with ME/CFS.

REFERENCES

1. Myhill, S., Booth, N. E., and McLaren-Howard, J. (2009) Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med 2, 1-16

2. Booth, N. E., Myhill, S., and McLaren-Howard, J. (2012) Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med 5, 208-220

3. Birch-Machin, M. A., Briggs, H. L., Saborido, A. A., Bindoff, L. A., and Turnbull, D. M. (1994) An evaluation of the measurement of the activities of complexes I-IV in the respiratory chain of human skeletal muscle mitochondria.
Biochem Med Metab Biol 51, 35-42