They figured out a thing!
September 17, 2023 6:58 PM Subscribe
She wrote to a scientist about her fatigue. It inspired a breakthrough: Her dogged efforts lead to a new scientific discovery that may help others with long covid and other chronically fatiguing illnesses (For those who aren't reading things that include animal research, this contains animal research) (Archive.org, abstract)
Significance
Chronic fatigue is a debilitating symptom that affects many individuals, but its mechanism remains poorly understood. This study shows that endoplamic reticulum (ER) stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance. Alleviating ER stress decreases WASF3 and restores mitochondrial function, indicating that WASF3 can impair skeletal muscle bioenergetics and may be targetable for treating fatigue symptoms.
What do you know, mitochondria really is the powerhouse of the cell.
posted by Joakim Ziegler at 12:56 AM on September 18, 2023 [6 favorites]
posted by Joakim Ziegler at 12:56 AM on September 18, 2023 [6 favorites]
Archive link for the WaPo article. Can you add fibromyalgia to the tags please? Also a fatigue causing illness. I’m so glad more research is coming out around fatigue, it is such a limiting illness/symptom.
posted by ellieBOA at 1:23 AM on September 18, 2023 [4 favorites]
posted by ellieBOA at 1:23 AM on September 18, 2023 [4 favorites]
The abstract says that in their tests they triggered overproduction of WASF3 in the lab by stressing the endoplasmic reticulum using endotoxin, which Google tells me is "the main component of the outer membrane of the cell wall of Gram-negative bacteria", which, again from the abstract, is "well known to be associated with fatigue in humans."
But it sounds like in her case they haven't yet found the cause of WASF3 overproduction? Underlying cause still a mystery?
posted by clawsoon at 3:10 AM on September 18, 2023 [2 favorites]
But it sounds like in her case they haven't yet found the cause of WASF3 overproduction? Underlying cause still a mystery?
posted by clawsoon at 3:10 AM on September 18, 2023 [2 favorites]
This is wonderful news. I was wondering if long covid would lead to ME getting more attention. It's been shockingly understudied in the past. I knew a surprising number of children, teens, and young adults who had it while I was a growing up and it's just awful to see someone go from living a normal happy life to unable to even walk across a room or have a conversation without taking a day to recover.
posted by EllaEm at 4:47 AM on September 18, 2023 [2 favorites]
posted by EllaEm at 4:47 AM on September 18, 2023 [2 favorites]
Going further down the endotoxin rabbit hole, here is a researcher who's proposing dosing health people with endotoxin in order to study inflammation-associated depression.
posted by clawsoon at 4:54 AM on September 18, 2023 [2 favorites]
posted by clawsoon at 4:54 AM on September 18, 2023 [2 favorites]
This is fascinating. Apparently the drug they are experimenting with as a theraputic is an experimental drug called salubrinal: source
posted by being_quiet at 6:54 AM on September 18, 2023
posted by being_quiet at 6:54 AM on September 18, 2023
I was wondering if long covid would lead to ME getting more attention.
I bet it has, but that isn't why they figured out this thing: "In 2016, she was intrigued by a journal article about Li-Fraumeni syndrome written by Hwang."
posted by aniola at 7:30 AM on September 18, 2023
I bet it has, but that isn't why they figured out this thing: "In 2016, she was intrigued by a journal article about Li-Fraumeni syndrome written by Hwang."
posted by aniola at 7:30 AM on September 18, 2023
The online ME community is definitely talking about this. Even if it only described the mechanism in a subset of patients it would be a huge break through to prove that there is a biomechanical reason behind the exercise intolerance (rather than a biopsychosocial one).
Sounds like the researcher is looking into a clinical trial with an ALS drug. It's a fairly expensive drug so maybe that will entice some pharmaceutical company to get behind it.
Here's a copy of the full paper if anyone is interested.
posted by mosessis at 8:04 AM on September 18, 2023 [3 favorites]
Sounds like the researcher is looking into a clinical trial with an ALS drug. It's a fairly expensive drug so maybe that will entice some pharmaceutical company to get behind it.
Here's a copy of the full paper if anyone is interested.
posted by mosessis at 8:04 AM on September 18, 2023 [3 favorites]
This is great. The other missing piece is the role that gender plays in this. I mean apart from its role in why the medical field just straight up ignores the whole issue.
Seriously made my day over here. Just seeing any progress give me so much optimism! Getting the whole issue of chronic fatigue getting dragged out of the shadows and taken seriously. It’s like FINALLY - it isn’t just women lounging on their fainting couch.
posted by zenon at 8:05 AM on September 18, 2023 [5 favorites]
Seriously made my day over here. Just seeing any progress give me so much optimism! Getting the whole issue of chronic fatigue getting dragged out of the shadows and taken seriously. It’s like FINALLY - it isn’t just women lounging on their fainting couch.
posted by zenon at 8:05 AM on September 18, 2023 [5 favorites]
This is an amazing story. That research team is headed by a very talented, open minded and determined physician.
posted by bluesky43 at 9:04 AM on September 18, 2023 [2 favorites]
posted by bluesky43 at 9:04 AM on September 18, 2023 [2 favorites]
This is fascinating. Apparently the drug they are experimenting with as a theraputic is an experimental drug called salubrinal: source
The rumour is that the drug they want to trial initially is Relyvrio (a very expensive drug for ALS that's actually a combination of a supplement called TUDCA and another drug, but the whole question of whether it even works in ALS is kind of up in the air). Salubrinal was used in the experiments behind this paper, but isn't an approved drug, so would be a much larger project to prove the safety of, etc.
posted by ssg at 9:12 AM on September 18, 2023 [4 favorites]
The rumour is that the drug they want to trial initially is Relyvrio (a very expensive drug for ALS that's actually a combination of a supplement called TUDCA and another drug, but the whole question of whether it even works in ALS is kind of up in the air). Salubrinal was used in the experiments behind this paper, but isn't an approved drug, so would be a much larger project to prove the safety of, etc.
posted by ssg at 9:12 AM on September 18, 2023 [4 favorites]
As ssg said while I've been typing, scuttlebutt from Brian Vastag, the article author, on Science 4 ME is "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."
Relyvrio is a combination of 3g sodium phenylbutyrate and 1g TUDCA. TUDCA was the other substance they found reduced ER stress in the paper.
More about salubrinal, the other experimental compound, from 2005.
posted by jocelmeow at 9:44 AM on September 18, 2023 [4 favorites]
Relyvrio is a combination of 3g sodium phenylbutyrate and 1g TUDCA. TUDCA was the other substance they found reduced ER stress in the paper.
More about salubrinal, the other experimental compound, from 2005.
posted by jocelmeow at 9:44 AM on September 18, 2023 [4 favorites]
I am hopeful that this continues into some sort of treatment. I would love to also see more info about how this may affect other symptoms of ME/CFS, etc. Like gastro, brain fog, chronic pain, etc. I've definitely been seeing things about mitochondria being a key on my timelines recently.
I wonder if this is a similar mechanism to this older study that was showing promise for testing for ME/CFS (was there more to this beyond this small study? I remember it at the time but don't remember anything after.)
posted by Crystalinne at 11:06 AM on September 18, 2023
I wonder if this is a similar mechanism to this older study that was showing promise for testing for ME/CFS (was there more to this beyond this small study? I remember it at the time but don't remember anything after.)
posted by Crystalinne at 11:06 AM on September 18, 2023
Crystalinne, the "nanoneedle" test that article refers to seems to not have worked out. No one ever really said it didn't work and there were a bunch of weird excuses about why they couldn't test it properly, but everyone involved seems to have moved on to other things, so I think the assumption has to be that it didn't work. It wasn't really ever clear what, if anything, the test was even supposed to be measuring. A weird episode, frankly.
posted by ssg at 11:37 AM on September 18, 2023 [1 favorite]
posted by ssg at 11:37 AM on September 18, 2023 [1 favorite]
Huh, thanks for the update! I'd been wondering what happened since I'm wary of small studies and hadn't heard anything after. Perhaps this newest finding could create more testing protocols and help people with diagnosis as well as treatments. Right now it takes years to decades if at all and makes it hard to get any answers.
posted by Crystalinne at 12:10 PM on September 18, 2023
posted by Crystalinne at 12:10 PM on September 18, 2023
This one probably won't directly lead to a test as only 9 out of 14 of the ME patients in the study (who were pretty scrupulously selected for the NIH ME study) had high WASF3 — and it's a pretty invasive test since it uses a muscle plug — but maybe it's a start that will lead to something else.
posted by ssg at 2:35 PM on September 18, 2023 [2 favorites]
posted by ssg at 2:35 PM on September 18, 2023 [2 favorites]
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posted by ssg at 7:28 PM on September 17, 2023 [37 favorites]