Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) 2012 Booth et al

Discussion in 'ME/CFS research' started by Andy, Jul 30, 2023.

  1. Andy

    Andy Committee Member

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    Abstract

    The objectives of this study are to test the hypothesis that the fatigue and accompanying symptoms of Chronic Myalgic Encephalomyelitis/Fatigue Syndrome are in part due to defects in energy provision at the cellular level, and to understand the pathophysiology of the defects so that effective medical intervention can be implemented.

    We performed an audit of 138 patients (ages 18-65) diagnosed with ME/CFS and attending a private practice. The patients and 53 normal, healthy controls had the ATP Profile test carried out on neutrophils from a 3-ml venous blood sample. This test yields 6 numerical factors that describe the availability of ATP and the efficiency of oxidative phosphorylation in mitochondria. Other biomedical measurements, including the concentration of cell-free DNA in plasma, were made. The results of the audit are compared with the controls and a previous cohort of 61 patients.

    We find that all patients tested have measureable mitochondrial dysfunction which correlates with the severity of the illness. The patients divide into two main groups differentiated by how cellular metabolism attempts to compensate for the dysfunction. Comparisons with exercise studies suggest that the dysfunction in neutrophils also occurs in other cells. This is confirmed by the cell-free DNA measurements which indicate levels of tissue damage up to 3.5 times the normal reference range. The major immediate causes of the dysfunction are lack of essential substrates and partial blocking of the translocator protein sites in mitochondria. The ATP Profile is a valuable diagnostic tool for the clinical management of ME/CFS.

    Open access, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403556/
     
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  2. Andy

    Andy Committee Member

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    "The patients attended a private practice specializing in ME/CFS and all satisfied the Centers for Disease Control (CDC) diagnostic criteria for CFS [5]. A review of the clinical notes shows that most, if not all, patients also satisfied the more stringent ICCME"
     
  3. Amw66

    Amw66 Senior Member (Voting Rights)

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    This is the test which could not be replicated, though I think there were some aspects changed in the attempt ?
    My daughter and aunt both had ATP profile tests done early in illness .
    There were interesting aspects relative to translocator protein ( aunt ) , low B3, low magnesium ( daughter) , and ATP levels.
    My daughter was basically chucking ATP out of cells in bucket loads . I didn't understand this until I realised it wasn't so much to do with energy as signalling . It was a distress call, which would activate AMPK and in doing so , a host of other pathways.

    The uncanny aspect was how accurate the energy value , which correlated to Bell scale, was. It was spot on.
     
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  4. Hutan

    Hutan Moderator Staff Member

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    I know this test was discredited, although I believe it was by Julia Newton's team. Some of her papers have been problematic and her stance on the applicability of BPS ideas to ME/CFS is well less than clear. My vague impression of the people involved in doing the Myhill-promoted test was that they were genuine, even if they were actually mistaken - although I didn't spend much time looking at it.

    Has the idea of cell-free DNA (in urine, blood, CSF) being higher in people with ME/CFS been ruled out (or replicated) in other studies? It seems like something obvious that will have been looked at often. Are there any issues to do with sample preparation that might affect findings?

    Similar for levels of cell-free ATP.

    @Andy, did you post this 2012 study for a particular reason?
     
    Last edited: Jul 31, 2023
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  5. Hutan

    Hutan Moderator Staff Member

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  6. Hutan

    Hutan Moderator Staff Member

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