WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome

[Andryr]

i fixed my me/cfs by fixing microbiome

What did you do exactly to fix it?

 

[skinnybane]

What did you do exactly to fix it?

Keep in mind that it applies to my specific problems which were high Bacteroides, and low firmicutes mostly.

https://www.reddit.com/r/covidlonghaulers/comments/1h72h5z

 

[Florida Guy]

I think this is a major discovery. A molecule that causes fatigue and its found mostly in me/cfs patients and when the molecule (wasf3) was counteracted, the fatigue went away. Countering it seems to be difficult since it has not lead to a cure yet.

This could lead to a test that could positively identify ME or show that its not present. Another thing this could lead to is finding out how exactly it takes away energy and what things could counteract that. This reinforces my view that within 10 years there will be a treatment for most forms of the disease.

 

[Paraprosdokian]

Wanted to share some research on curcumin which may alleviate the endoplasmic reticulum stress identified in this paper. The gist is that while there is some research suggesting curcumin reduces ER stress, there are good reasons to doubt this.

There are a number of papers to suggest curcumin has anti-ER properties. This paper summarises a lot of these papers: https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.767493/full#B12

Confusingly, curcumin has also been found to kill cancer cells by triggering ER stress. How can one compound cause ER stress in some cells but reduce it in others?

This makes me wonder how accurate the studies are. My theory is that the curcumin is interfering with the tests scientists are running and that is causing them to appear to trigger or reduce ER stress (depending on what the researchers' hypothesis is). That is backed by this paper which lists the various ways curcumin can interfere with assays used to measure the level of chemicals in cells: https://pmc.ncbi.nlm.nih.gov/articles/PMC5346970/

That paper points out that there have been over 120 clinical trials run on curcumin and no double blinded, placebo trial has found any significant effect. It "provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead".

I asked ChatGPT and Claude about my hypothesis. ChatGPT thought curcumin could both increase and decrease ER stress - this may have been because it didnt want to contradict its prior answer. It also agreed with my point about curcumin interfering with assays but pointed out some of the studies did try to avoid this through various methods. E.g. one paper used a luciferase essay which is less suspectible to interference by curcumin. Overall ChatGPT had moderate confidence that curcumin did decrase ER stress generally and increase it in cancer cells.

By contrast, Claude agreed that the contradiction was difficult to justify and we should be cautious.

Another factor to consider is curcumin has low bioavailabililty. The doses used in the studies far exceed what you can get through supplementation. That means that eating curcumin is unlikely to affect our cells. So if you do take it, make sure you can a version with enhanced bioavailability.

Curcumin also interferes with other drugs and supplements so be careful if oyu are taking it.

 

[godlovesatrier]

Tudca is a lot better if tolerated for er stress.

 

[SWAlexander]

Several supplements are now under scrutiny due to ongoing concerns. The focus now is a potential link to elevated arterial lactate levels and muscles.
On this subject, there are quite a few publications:

Example 1​

Elevated Arterial Lactate Concentrations Early After Coronary Artery Bypass Grafting Are Associated With Increased Anaerobic Metabolism in Skeletal Muscle
https://www.sciencedirect.com/science/article/abs/pii/S1053077014003553​

 

[Aidan Walsh]

What was the medicine used in the female WASF3 patient at the NIH study published in 2023?

Did she fully recover yet? I have the Genetic mutation for TP53 heterozygous for Li-Fraumenia. I checked the other 3 genes I was negative for them. thank you all

 

[Aidan Walsh]

I think this is a major discovery. A molecule that causes fatigue and its found mostly in me/cfs patients and when the molecule (wasf3) was counteracted, the fatigue went away. Countering it seems to be difficult since it has not lead to a cure yet.

This could lead to a test that could positively identify ME or show that its not present. Another thing this could lead to is finding out how exactly it takes away energy and what things could counteract that. This reinforces my view that within 10 years there will be a treatment for most forms of the disease.

I cannot see how this will take away the Cancer gene TP53 mutation for LI-Fraumeni which causes so many lethal Cancers & a slow ride to AML Acute Myeloid Leukemia

 

[Aidan Walsh]

Tudca is a lot better if tolerated for er stress.

Is it spelled TUDCA or TUDKA? What was the treatment she used with Hwang NIH for WASF3 the woman treated? @Violeta xx

 

[Aidan Walsh]

@Violeta

Isn't tudca a fairly common supplement ? something to do with artificial bile, surely some of us would have taken it since we have various stomach related problems, personally I did not but I took digestive enzymes, promotility stuff, many antiviral or antibacterial / antifungal herbs, acid boosters, random vitamins etc.

All that you took are some of the single treatments used for the Wilkott-Aldrich Syndrome WASF3

 

[Aidan Walsh]

datadragon​

Is it not amazing that we, the patients, understand the content of these papers while doctors don´t?​

@SWAlexander What was the treatment used by Dr. Hwang on the female Wilkott-Aldrich patient the Albany lawyer 2003 paper NIH Li-Fraumeni/Wilkott-Aldrich? I see my Doctor on Wednesday. thanks so much