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Research news from Bhupesh Prusty
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Jonathan Edwards
Senior Member (Voting Rights)
That would be an autopsy, but basically yes, biopsies of living brain are only justified if you have very good reason to think that you have encephalitis or tumour in a potentially dispensable area. Effectively that means you need gross neurological signs on physical examination suggesting that a particular area is already pretty much destroyed.
I am afraid this all sounds a bit unrealistic. Tweeting the results of single experiments does not seem to me to be a good idea in biomedical science. Usually by next month you have found you cannot get the same result twice.
Jonathan Edwards
Senior Member (Voting Rights)
I had assumed that he was just talking about some soluble or suspendible factor of the sort that has been proposed to explain previous results with ME plasma affecting normal cells. (Maybe a protein or cell fragment.)
Jonathan Edwards
Senior Member (Voting Rights)
I am sceptical of that approach. We have not so far ever known that mitochondrial function is affected in ME. It is a speculation that is quite difficult to marry with the clinical picture.
And if you fail to find something you cannot really just say, oh we did not need to find it anyway for it to be the problem.
This looks like doing science backwards - deciding what the answer is and then trying to force all the results to fit.
I will be as pleased as anyone if something comes out of this research but I think ME research deserves a better approach than this. Something that recognises the true level of our ignorance and does not raise undue expectations.
Hip
Senior Member (Voting Rights)
I hope Dr Prusty and his team use suitably sensitive methods for detecting viruses, and use a system which can detect all viruses.
Sometimes even with the right testing, finding viruses in the tissues can be tricky:
When John Chia first tried to find enterovirus in the brain tissues of an enterovirus ME/CFS patient who committed suicide (whose family had donated the body to science, to help advance ME/CFS research), Chia was unable to find evidence of enterovirus RNA in the brain, even using sensitive RT-PCR.
But Dr Chia later remembered a phenomenon whereby viral RNA may bind to chromosomal DNA, thus preventing RT-PCR from detecting the RNA. (I don't know the name of this phenomenon, because I couldn't find any further details — if anyone knows more about it, please let me know).
So Dr Chia used the DNase enzyme to digest the chromosomal DNA in his brain tissue samples, and after doing so, he was then able to detect enterovirus RNA in the frontal cortex and pontomedullary junction (in the brainstem) of this ME/CFS patient brain. Ref: here.
Sometimes even with the right testing, finding viruses in the tissues can be tricky:
When John Chia first tried to find enterovirus in the brain tissues of an enterovirus ME/CFS patient who committed suicide (whose family had donated the body to science, to help advance ME/CFS research), Chia was unable to find evidence of enterovirus RNA in the brain, even using sensitive RT-PCR.
But Dr Chia later remembered a phenomenon whereby viral RNA may bind to chromosomal DNA, thus preventing RT-PCR from detecting the RNA. (I don't know the name of this phenomenon, because I couldn't find any further details — if anyone knows more about it, please let me know).
So Dr Chia used the DNase enzyme to digest the chromosomal DNA in his brain tissue samples, and after doing so, he was then able to detect enterovirus RNA in the frontal cortex and pontomedullary junction (in the brainstem) of this ME/CFS patient brain. Ref: here.
Hip
Senior Member (Voting Rights)
Being dead is a distinct advantage when taking brain tissue biopsies! Sadly it's often ME/CFS patients who have committed suicide who have their brain tested for viruses, if the family donates the body to science in order to further ME/CFS research.
I just wonder if the findings in Alzheimer's disease may provide a template. Here a bacteria (gingivalis) produces a protein (gingpains) which cleaves a protein produced by the person/patient i.e. Apolipoprotein E (APOE). Presumably there's a cascade affect resulting from the cleavage of APOE ---leading to Alzheimer's. This discovery was the result of a GWAS study --- Chris Pointing has applied for funding for a GWAS study for ME!
So possibly Bhupesh has found a consequence/downstream affect (mtichondrial fragmentation); if so then finding the upstream cause seems like a challenge!
Ron Davis's group were trying to identify the something in the blood; success in identifying that might clarify Bhupesh's findings.
So possibly Bhupesh has found a consequence/downstream affect (mtichondrial fragmentation); if so then finding the upstream cause seems like a challenge!
Ron Davis's group were trying to identify the something in the blood; success in identifying that might clarify Bhupesh's findings.
rvallee
Senior Member (Voting Rights)
The networking mitochondria thing is already understood?
Hard to say whether it's specific to an active herpesvirus or ME but they are clearly working differently, not connecting to one another, and adopting different shapes. That stuff is already known and understood? How mitochondria are normally long, active and connecting to one another vs how they bundle up and seem to isolate themselves in the presence of either an active HHV6 infection or, it now seems, ME blood?
Seems like having a hypothesis and testing it. That seems fine and proper science as long as they try to prove it wrong, not merely find positive evidence you can squint at. It's still a downstream effect given the unknown factor in the blood, not a fully-fledged solution presented as the answer.
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1hullofaguy
Established Member
I think a clear difference is though the reversibility of ME vs the lasting neurological damage found in Alzheimer’s, especially with spontaneous remissions in ME. I’m unsure however if that would preclude this etiology.
I agree with everything you have written including "I’m unsure however if that would preclude this etiology". This was just an "idea" perhaps there is something analogous to "gingpains"; however, as you highlight this would have to be reversible ---- derived from a disrupted microbiome?
Check out Chris Armstrong's 2016 webinar.
I'm just very unsure that the something in the blood is causing the me/cfs symptoms and not way down stream leading to some minor changes. I still think it'll be useful to figure out what it is, and maybe reverse engineer that to find out what's going on.
I'm actually kind of surprised we haven't figure out that yet after what feels like 3-4 years. But, perhaps that is due to my naivety in biomedical research.
I'm actually kind of surprised we haven't figure out that yet after what feels like 3-4 years. But, perhaps that is due to my naivety in biomedical research.
I think part of the problem of identify what it is, is that you need resources i.e. relatively good mass spectrometer (Stanford and really most significant research groups have them) and a means of fractionating the plasma - to isolate the something in the blood. Ron Davis, in conversation with Ben H (December 2019 - OMF News), explains that they are upgrading the nano-needle to fractionate the plasma - $30,000 to change it to a multichannel device/multiple samples (currently just 2 samples can be run)--- that is how broke ME researchers are! Also, Ron pointed out years ago that chemicals can do different things in different places - using ATP inside/outside cells as an example. So identifying what it is can be tricky --- even if you look!
But yea I'm with you - this shouldn't have taken this long i.e. to get started - original publication December 2016 - https://www.ncbi.nlm.nih.gov/pubmed/28018972
There's a thread here regarding an EU Petition for public funding for biomedical research, supported by ME Acton [https://www.s4me.info/threads/eu-pe...ding-for-me-research.10363/page-7#post-233722]
ME Action also lobby in the UK, USA --- + other charities lobby for funding OMF, Solve, EMERGE ---
Further thought, gingpains, produced by bacteria (gingivalis), cleave cytokines --- so I guess they are trying to beat the immune system ---- Bupesh is looking for compounds, produced by virus (& bacteria?) which try to beat the immune system by fragmenting mitochondria.