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

Sorry if I could ask here since I missed so many posts, are there any ideas as to why in some of our cells there is ER stress and the UPR can’t bring things back to normal? Why is that and what caused the ER stress to begin with?

 

I'm not sure any good ideas have been developed yet. I'm wondering about abnormal lipid handling or hypoxia and I noted here that in Covid, one of the ER stress sensors (GRP78/BiP) binds to spike protein. Perhaps a mitochondria to ER stress response may become pathological after initial mitochondrial impairment and form an uncontrolled positive feedback.

I've posted some possibly relevant papers with summaries under the er-stress tag.

 

Quickly leaving the template here, if others desire to send to NHLBI Director as well:

Message Template:

To: NHLBIinfo@nhlbi.nih.gov; gibbonsgh@mail.nih.gov

Subject: Please support ME/CFS research conducted by Dr. Paul Hwang

Dear Dr. Gary Gibbons,

I am writing to you in your capacity as director of the National Heart, Lung and Blood Institute (NHLBI). I read about Dr. Paul Hwang's potential breakthrough on WASF3 in ME/CFS, and his desire to run a drug trial, via The Washington Post, "She wrote to a scientist about her fatigue. It inspired a breakthrough."

Most exciting, Dr. Hwang now wants to conduct a drug trial.

My urgent request is that you please expedite your efforts to fund his lab — and specifically this trial.

The lack of research into ME/CFS over the decades has likely contributed to the current lack of treatments for Long COVID, as ME/CFS and Long COVID are quite similar or perhaps the same illness. For those who have been suffering from pre-COVID ME/CFS for decades without hope and for those suffering from Long COVID for going on four years, please make up for the decades of disbelief and neglect and deliver us the help that we have been denied for so long.

Thank you,

xxxxxxxxx'

 

Just noting here that the Independent (UK) picked up the story (they just rewrote mine, haha). So it's getting some attention in the UK too, which is good. Also, Francis Collins wrote to me this morning to say he read the article & liked it. He's retired, or I guess semi-retired (still has a lab...I don't know what he does there). So he's still paying attention I guess.

https://www.independent.co.uk/stude...ast-cancer-long-covid-research-b2414180.html#

 

I sent something with the help of ChatGPT. It's pretty good for stuff like this, just asking it to rewrite the message so that it preserves its intent but sounds different enough that it doesn't seem like a copy-paste. Easy peasy.

 

@B_V From a member on Phoenix Rising forum: “Well - I added lead researcher Paul Hwang to the email and he replied to me already! He thanked me for my support and said that he was certain that Drs. Gibbons and intramural scientific director Dr. Richard Childs would support the planned exploratory treatment trial later next year.”"

 

Love that you included all those kisses at the end

 

I have looked into this drug and it's supposed to slow the effects of ALS not reverse it. Would it be doing similar here, i.e preventing deterioration, or would it be aiming to improve patients functioning?

 

Paul Hwang says he's been "deluged" with emails from patients and he's trying to respond to each one with a prepared response. So I'm guessing most folks will get the same message from him.

He also says the support from the community is "greatly appreciated."

 

@B_V if felt appropriate, that might be worth highlighting on social media as a marker of problem scale.

 

So patients DO send mails to researchers!

 

From David systrom work

"muscle biopsy done at Baylor found citrate synthase deficiency in 10/11 patients"

How would that fit with these WASf3 findings?

 

Just quickly sharing Dr. Hwang's reply after I forwarded my correspondence to NIH on his research.

"Thank you very much for your support, Mr. Hanlon. Will keep doing what I can on my side."

And this reply from NIH RECOVER, as I copied them to at least have this research on their radar:

"Thank you for your message to the National Institutes of Health (NIH) about the research of Dr. Paul Hwang at the National Heart, Lung, and Blood Institute (NHLBI). Indeed, NHLBI already funds Dr. Hwang’s intramural research, including the study you mentioned. You can read more about Dr. Hwang and his research on the NHLBI website.

"Those working on RECOVER, including experts in post-infection conditions, believe that their research could benefit not only people with long COVID, but also shed light on other post-infection conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), dysautonomia, and others. For more information about ME/CFS, the RECOVER Initiative, and long COVID, view our FAQs: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Fact Sheet. Thank you again for reaching out to NIH."

 

Sharing with permission, a message by Dr. Hwang, @B_V. I thought it may be beneficial for visibility for the community to view:

"I have received a large volume of emails since the publication of the Washington Post article by Brian Vastag about my research. With a desire to be responsive, I have listed below information that addresses common themes within the emails I am receiving.

1) While our research study is not currently recruiting clinical participants, our work continues in the lab to better to understand the “biology” of the protein called WASF3, which may give us some ideas about the mechanism and/or etiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

2) To be clear we do not believe WASF3 is the cause of ME/CFS but is one of the factors mediating the energy deficiency in muscle. Understanding its biology and regulation, for example, may help us understand the causes of ME/CFS.

3) We observed increased levels of WASF3 in a subset of the 14 ME/CFS patients. Please understand this is a small sample size. So WASF3 levels in muscle may explain fatigue in only a subset of patients with ME/CFS diagnosis. There could be other factors mediating fatigue in people with ME/CFS.

4) There are no clinical or blood tests available to check for WASF3 levels, and our experiments have not observed WASF3 in blood. In the publication reported publicly through the Washington Post, we used skin biopsy cells grown in tissue culture and muscle tissue samples obtained by needle biopsy to measure WASF3 levels. These tests cannot be done in the clinics by your physicians. But even if they could, more studies are needed in order to understand the meaning of these results.

5) We studied WASF3 levels only in patients diagnosed with ME/CFS. We have not examined patients with Long COVID, so it remains unknown whether the protein WASF3 is involved in Long COVID. Future studies are needed to address this question.

6) As you may know, there are many different medical conditions associated with fatigue. My research examines only one, ME/CFS. I cannot speak to the association of the WASF3 protein to other conditions. My research will continue to focus on the ME/CFS condition through other studies – including exploratory studies.

7) As far as next steps, it is difficult to anticipate all the different issues that will need addressing with getting a clinical trial approved. So, I hesitate to predict timing.

8) In an exploratory treatment study, we would plan to focus on the ME/CFS condition. Therefore, I would expect that an inclusion criterion to participate might be having had a formal diagnosis of ME/CFS after evaluation by a physician at an outside medical center, but again it is difficult to anticipate the issues that might arise in the design and approval processes of a clinical study.

Patient input is critical to better understanding ME/CFS. The published research article provides important insights that will serve to encourage more research into ME/CFS and advances our understanding of this debilitating condition.

Sincerely,

Paul Hwang, MD, PhD"

 

that all seems responsible & sensible that all sounds, and courteous to the community to not get overinflated/hopes up unnecessarily i respect that

 

They really wanna do a treatment trial! Yes!

 

Also quickly sharing Dr. Hwang’s reply to me today.

I asked, “Do you think that Dr. Gibbons and NHLBI will support your pursuit for an exploratory treatment trial in this research?“

Dr. Hwang: “Yes, I am sure that our clinical protocol once it is developed will be supported. I believe the NIH realizes the importance of considering and following up on every treatment lead for ME/CFS, including our specific finding.”

 

Good letter. Seems like a cautious guy. I wish people would stop bombarding him with dumb questions like where they can get tested and let the man work.

 

Dunno, think it wouldn't be hard for him to set up a filter if it gets too distracting. And I'd imagine it's nice to be appreciated.

 

It may be annoying to deal with after a while, but don't underestimate the power that thousands of people can have in emphasizing the importance of something like this.

Maybe it's different in medical academia, though I doubt it, but generally speaking researchers get very little attention for their work. Unless it's a giant seminal paper, or a fluke that propels them to instant public recognition, most will never hear any interest from the public. Not even once.

So much that most academics will answer any question you ask them about any paper they published, they'll often even send you copies if you ask, even if it's behind a paywall. Not that they have so much free time, but that it happens so rarely that it almost feels like a minor award.

Of course the biopsychosocial ideology is a very different beast, they do get a lot of justifiably angry feedback from the public, but I don't consider them to be real researchers anyway. They're academics in name only. Quacks deserve criticism and they are getting it, they just can't process why. Real researchers almost never get any attention whatsoever, especially not positive.

So you can bet that this is getting a lot of buzz in the lab where they work. This is the equivalent of getting crowded by hundreds of fans wanting to speak with you and asking for photos as an artist. It does not happen often.