(A) Epigenetic code dynamics
In 2019 we have shown in ME/CFS patients changes in the dynamics of the epigenetic code - a DNA code that responds to environmental /nutritional and disease influences – this is a genomic regulatory system linked to changes in gene expression around the on/off switches of genes. This could explain the hypometabolic state in the 2016 Stanford University study of plasma metabolites, and our own studies of the expression profiles of the genes that suggested ME/CFS patients are in a ‘state of hibernation’. This has enabled us to deduce which individual genes are affected, and how that translates into lower efficiency of biochemical pathways that might be sustaining ME/CFS. Now in 2020/2021 we are examining epigenetic changes through ‘relapse recovery cycles’, and seeking to see whether it can explain the core symptom of ME/CFS, ‘post exertional malaise’
At the end of 2018 we published an hypothesis for how ME/CFS might be being sustained as an ongoing illness involving the hypothalamus and the stress centre within it. This has been featured recently by Health Uprising. 2019 brought new ideas relevant to this hypothesis and in 2020/2021 we are trying to connect these and test an hypothesis for ME/CFS that a stress hormone produced in the stress centre of the hypothalamus, and a defective receptor for it, causes excessive production of serotonin. In 2020/2021 we are analysing DNA samples from our ME/CFS patients for evidence of mutations in a gene responsible for degrading tryptophan –the precursor to serotonin - and whether ME/CFS patients have excessive serotonin levels.
(C) Energy production
In 2019 we determined by mass spectrometry that there were major changes in many protein components of the energy producing complexes and regulators of damaging reactive oxygen species in the energy powerhouses of the cell - the mitochondria. We can deduce that the mitochondria are trying harder to produce energy because we think the key last step is somewhat defective. This work has suggested that oxidative stress is significant in ME/CFS and has given us direction for a new study in 2021 on its extent in ME/CFS and whether it can be alleviated by the powerful antioxidants, CoQ10 and MitoQ.
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