Livestream Alan Light, PhD today at 6pm MST "New findings suggest that multiple mitochondrial mutations create susceptibility for ME/CFS"

BeautifulDay

BeautifulDay

Established Member (Voting Rights)
Wigglethemouse gave me a heads-up about this live event later today.

Bateman Horne Center
"Please join us for our free live stream event, tomorrow Weds. Dec. 5th 6pm MST. Mutations in Energy and Autoimmune Genes Cooperate to Cause ME/CFS" with Alan Light, PhD. New findings suggest that multiple mitochondrial mutations create susceptibility for ME/CFS. Watch the event from our Facebook page. Q&A to follow."

https://www.facebook.com/search/top/?q=bateman horne center&epa=SEARCH_BOX
 
Trish said:
Unfortunately for us in the UK, that's 1 am. I hope it will be made available afterwards for us to watch. If anyone does watch it live, do report back here if you can.
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Recording appears to be on Facebook now. Haven't watched it yet but video started playing ok after a few seconds of a confusing message saying live stream will start soon (confusing because live stream long past).
 
Some comments based on the "Liver Injury" hypothesis and given Dr. Light's presentation :

A first note is that many people asked whether the observed difference in frequency of mutations between ME/CFS patients vs controls may not be statistically significant.

1) CPT2 - Carnitine palmitoyltransferase, as stated in the presentation it can cause liver disfunction

It is interesting that CPT2 is a key component of beta fatty acid oxidation (β-FAO) and a PPARa agonist upregulates CPT-2 :

Metabolomic analysis revealed that alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis resulted in the accumulation of serum long-chain acylcarnitines and triglyceride, and the reduced expression of four fatty acid β-oxidation (β-FAO) relevant genes (Cpt1b, Cpt2, Mcad and Hadha), indicating the disruption of β-FAO. The increase of acylcarnitines in hepatic cell resulted in the enhanced expression of anti-oxidative genes glutathione S-transferases (Gsta2 and Gstm3) directly. As direct PPARα-regulated genes, Cpt1b, Cpt2, and Mcad were up-regulated after pretreatment with PPARα agonist, fenofibrate, indicating the improvement of β-FAO.

https://www.nature.com/articles/s41598-017-10524-6


2) HSPA1L - Heat shock protein

Heat shock 70 kDa protein 1L is a protein that in humans is encoded by the HSPA1L gene on chromosome 6.[5][6][7] As a member of the heat shock protein 70 (Hsp70) family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins.[7][8] Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation.[8][9] It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease.[8][9][10]

For those of you being on Phoenix Rising, ER Stress, Protein misfolding and the Unfolded Protein response (UPR) were part of this theory since 2015.

3) ATP7A : Wilson's Disease is mentioned. Copper is toxic to the liver. What is the prevalence of Wilson's Disease in ME/CFS Patients vs Controls ?

4) ACADS : Since one more Gene related to fatty acid beta-oxidation (β-FAO) is mentioned : Interestingly one of the main sites that β-FAO takes place is the Liver (others are heart and sceletal muscle)

From the following link : http://lipidlibrary.aocs.org/Biochemistry/content.cfm?ItemNumber=39187

We see the following figure where FAT/CD36 appears (noting that CPT2 appears that Dr Light has mentioned)


Screen Shot 2018-12-06 at 09.35.12.png




Interestingly, CD36 regulates Vitamin E absorption (Vitamin E also happens to be stored in the Liver).

https://www.researchgate.net/public...ith_plasma_vitamin_E_concentrations_in_humans



A good question would be : A lot of ME/CFS patients are checking their Vitamin D Levels (which is also stored in the liver) but not the levels of Vitamin A, E and K. Will we find deficiencies in other Fat-soluble vitamins in ME/CFS patients? Has any researcher looked at this very simple question ?

Very soon i will post more regarding Vitamins A and E since the potential role of Vitamin K has been extensively looked at.
 
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I have watched the webinar. I found it interesting, though for a genetic study the numbers so far are small, and the differences found between pwME and controls in frequency of some of the genes he listed was tiny. And presumably they cherry picked the ones that had a higher frequency in pwME.

His concluding slide was particularly interesting as it summarises the hypothesis he has developed as a result of his research:

Exposure to pathogens and other causes of inflammation can trigger increased or 'de novo' autoimmunity causing fatigue and post exercise malaise that does not remit because of the susceptibility created by mutations either inherited or acquired and epigenetic alterations.
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A few thoughts and questions on the presentation:
  • Question: Does anyone know if there is, or will be, a paper published about these findings?
  • They found quite a number of mutations that were more frequent in patients than controls. However, numbers were low and I wouldn't be surprised if some or most of those differences disappeared in a larger study.
  • However, numbers looked more convincing when they looked at combinations of mutations. Patients were much more likely than controls to have two separate mutations, for example one on a mitochondrial gene and second one on an autoimmune-regulating gene.
  • Rather than most patients having one specific mitochondrial mutation plus one specific autoimmune-regulating mutation, each affected patient could have any one out of a pool of possible mitochondrial mutations plus any one out of a pool of possible autoimmune-regulating mutations, so many different combinations are possible.
  • Question: Do other gene studies look at combinations in this way? And at pools of possible mutations? The reports I've seen all seem to be looking only for single mutations that are more frequent in the ME patients, never at combinations? I would assume that combinations are harder to find? And that the statistical signal of a combination would be weaker – or rather the signal for the individual mutations within a group would be weaker - and therefore more easily missed?
  • A few controls also had the combination mutations. Light speculated that these individuals may be at risk of getting ME in the future if they happen to become exposed to a trigger.
  • Question: I have long wondered something similar when reading other studies and looking at symptom overlap and outliers in the results. Are healthy control outliers actually future ME patients? Conversely, are ME patient outliers misdiagnosed and actually suffer from something else? Do any studies keep track of their outliers to see what happens to them, i.e.to see if ME patients later get re-diagnosed with another condition, and healthy controls come down with ME?
 
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