WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome, 2023 Hwang et al

Ash said:
Me too.
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I don’t know anything about how muscles work, but for me it seems that my underlying muscle strength is quite normal for a sedentary person. On a good day, I can access that strength.

But most of the time I have almost no effective strength at all and am often too weak to (for example) lift a glass to drink out of. But if I rest for a few weeks until the PEM lifts, my muscle strength is back to normal again (incidentally falsifying the deconditioning hypothesis).

It’s like the machinery is all working, but the power supply is usually switched off. On the rare days that the generator is functional, the machinery seems fairly normal. If the researchers tested the mice’s strength at the start (rather than after the exertion) then a normal finding doesn’t seem necessarily inconsistent with some ME experience.
 
Jaybee00 said:
Good article! @B_V

1) How to get tested for this outside of NIH (WASF3 over expression)?

2) Based on this small sample a significant percentage (35%) don’t have this issue but still are definitively diagnosed with MECFS—so maybe the non-WASF3 is a subset?

Slightly off-topic
3) Do you know if she received cyclophosphamide as part of her chemotherapy—and did she notice any improvement in her fatigue level with cyclophosphamide treatment?
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1) I don't think it's possible outside of a research setting.

2) So the numbers are a little tricky. The main measure of WASF3 was really between populations....the average in the entire ME/CFS cohort (14 patients w/ muscle biopsies examined) was significantly higher than the average in the controls. That's the measure that Paul thinks is more important. But yes, like all things with ME/CFS, there was variation and not everyone had elevated WASF3.

3) I don't know what chemotherapy she received.
 
This comment stood out to me —

Thank you, thank you for this excellent article. I, too, have CFS and possibly also long COVID. I have been subjected to horrific abuse from physicians who seem to be deeply invested in denying the existence of the disorder. One, working for a prestigious health care institution, told me that before he met me for the first time he saw on my record that I was a patient of the CFS Clinic and knew that nothing I said would be worthy of being taken seriously. What is it about this illness that it inspires actual hatred from those who have sworn to do no harm?
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dratalanta said:
But if I rest for a few weeks until the PEM lifts, my muscle strength is back to normal again (incidentally falsifying the deconditioning hypothesis).
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The decades long persistence of the deconditioning claim is going to go down as one of the most unscientific and disturbing in modern mainstream medicine.

A classic example of how people, even the most trained, resourced, and 'expert' of people, managed to completely fail to actually test their claim despite the existence of robust means to do so, to wilfully ignore the 800kg gorilla in the room being repeatedly pointed out by others, and just go on seeing what they wanted to see and nothing else.

Philosophers and historians of science, and morality, are going to build whole careers on studying this one.

What is it about this illness that it inspires actual hatred from those who have sworn to do no harm?​

It is beyond bizarre. It is grotesque moral failure at every level, from the individual clinician all the way up to global level institutions.

(Not every single one, of course, but overwhelmingly and persistently, for half a century, the profession has failed us big time.)
 
dratalanta said:
It’s like the machinery is all working, but the power supply is usually switched off. On the rare days that the generator is functional, the machinery seems fairly normal.
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Well said. My muscle strength switches on and off for no obvious reason. I try to lift small amounts of weights on good days to maintain some strength, small amounts are better than doing nothing, but I have days/weeks/months that I can't do 4 reps so it's full stop. Same with muscle balancing exercises, some days I'm almost normal but others I can't do anything.
 
Mij said:
From the article:

"The red flags that Twinam had an unrecognized chronic illness began after her suspected case of mono in high school. She says she feels she never fully recovered. One big tell: In college, after exercising, Twinam would not experience an endorphin rush.. Instead, she told her friends she “felt like garbage.”

Exactly what I experienced during sudden viral onset PVFS in 1992. I didn't feel like 'garbage', I felt very flat, no PEM just flat.
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I've played soccer/football for a number of years after I've got diagnosed and feeling flat turned into feeling like garbage at some point.
 
Solstice said:
I've played soccer/football for a number of years after I've got diagnosed and feeling flat turned into feeling like garbage at some point.
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How long did it take that garbage feeling to turn into PEM? Felt flat after exercising during PVFS, and then I went straight to getting PEM years later.
 
Mij said:
How long did it take that garbage feeling to turn into PEM? Felt flat after exercising during PVFS, and then I went straight to getting PEM years later.
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Very good question that I don't have an exact answer too. It's been about 13 years ago that I've stopped playing and at the time I didn't know about PEM, so I don't think I took much notice.
 
B_V said:
Paul Hwang is trying to get a clinical trial of Relyvrio going. It's an ALS drug and he has some evidence it can reduce overexpressed WASF3.
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I saw in an NIH media piece on the study that they were also looking at the ER stress inhibitor drug salubrinal and tested it on ME cells in the study and it reduced WASF3 as well as normalized mitochondria energy production.
 
@B_V thank you for all the hard work on this, and for providing the patient community a much needed dose of new discovery and reinvigorated hope. It’s nice to connect again in some way.

You and I originally met near your place in DC in 2013 when I was working at NIH and had recently gotten ME from a protracted viral infection and was trying to reach out to others for help. You were at WaPo and your ME had been deteriorating. Feels like a lifetime ago. Brian you and Beth were both very kind and helpful I wish all the best for you. I was able to continue working at NIH with tons of accommodations until 2021 severity progressed to mostly bedound and I had to stop my cancer research career. I hope you both are doing well in Hawaii.
 
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