Jesse2233
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Tumor protein p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. It appears to also repair damaged mtDNA (DNA specific to the mitochondria).
From a 2012 paper in the American Journal of Pathology:
In a talk given by Dr Alan Light on 2/1/2017, he discusses yet to be published findings that acquired mtDNA mutations were found present in 39 out of 40 ME/CFS patients. Cort has a good summary here.
This 2011 study from Johns Hopkins links ME/CFS severity in part to GPR41, a gene involved in p53 signaling. These findings tie into Dr Gerwyn Morris' 2012 hypothesis that the loss of p53 is a key mechanism in ME/CFS.
I've not seen this discussed anywhere on PR, but perhaps boosting p53 can treat the core pathology of the disease.
How might we do this?
Caveats:
Almost all of this is above my head and I could be making some key misconceptions, so I'd love to get the feedback of those with a science background
Tagging some potentially interested folks:
@alex3619 @Valentijn @Hip @nandixon @alicec @halcyon @Tunguska @JaimeS
Thanks!
From a 2012 paper in the American Journal of Pathology:
The p53 within the cell is helpful in maintaining normal mitochondrial function because p53 in the mitochondria enhances base excision repair of mtDNA damage, and a loss of cellular p53 reduces mitochondrial function.
In a talk given by Dr Alan Light on 2/1/2017, he discusses yet to be published findings that acquired mtDNA mutations were found present in 39 out of 40 ME/CFS patients. Cort has a good summary here.
This 2011 study from Johns Hopkins links ME/CFS severity in part to GPR41, a gene involved in p53 signaling. These findings tie into Dr Gerwyn Morris' 2012 hypothesis that the loss of p53 is a key mechanism in ME/CFS.
I've not seen this discussed anywhere on PR, but perhaps boosting p53 can treat the core pathology of the disease.
How might we do this?
- There is a Chinese cancer
drug(edit: gene therapy) called Gendicine which is designed to treat patients with tumors who have mutated p53 genes. It does this via a recombinant adenovirus engineered to express wildtype-p53. This in turn over-expresses genes coding for the p53 protein, and, in my laymen's understanding, boosts p53. Its side effects seem to be relatively mild.
Unfortunately this drug is only approved for use in China although I imagine there are ways to acquire it.
- A 2003 study in Nature reports that interferon gamma / beta stimulates p53 synthesis.
There has been a plethora of discussion on this board about ways to induce interferon and various studies and anecdotal stories showing benefit. For example: Dr John Chia's use of interferon to achieve full (albeit temporary) remissions, and the demonstrated effectiveness of Ampligen (an interferon inducer) to bring about near remissions.
Perhaps these drugs are effective (in part) because they stimulate p53.
- Finally a 2006 study from China shows that oxymatrine (another Dr Chia mainstay) up-regulates p53.
Caveats:
- A 2017 study published in BMC Medical Genetics (discussed here) found little evidence of mtDNA damage in ME/CFS patients.
- In 2016 Dr Ron Davis mentioned that "ME/CFS patients have a marked decrease in some of the Citric Acid Cycle metabolites while mitochondrial mutations generally cause an increase."
Almost all of this is above my head and I could be making some key misconceptions, so I'd love to get the feedback of those with a science background
Tagging some potentially interested folks:
@alex3619 @Valentijn @Hip @nandixon @alicec @halcyon @Tunguska @JaimeS
Thanks!
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