4 ms·

I wonder if any of these findings help us better understand me/cfs.

galangalalgol 2y ago
It has been my hope that the number of me/cfs cases would finally drive enough research into autoimmune disorders in general, that we might finally figure it out. It seems very poorly understood from an outside perspective.
- PaulKeeble 2y ago
  There is no funding and since Long Covid appeared the funding for ME/CFS has completely vanished. If Long Covid ME like illness is the same then ME/CFS is getting lots of research right now, on the other hand if they turn out to be different ME/CFS patients are getting completely ignored.
  - thenerdhead 2y ago
    Many ME experts are doing both. RECOVER is considering adding ME/CFS arms to its huge clinical trial platform. UCSF just added ME/CFS as a priority in their LIINC program. SARS-CoV-2 therapeutics won’t work on both but immune cell based ones may given they haven’t been tested in either yet. Both suggest a root cause of persistent viral antigen. Time will tell what works here.
    - Elinvynia 2y ago
      RECOVER is the biggest scam when it comes to research unfortunately. 90% of their studies are focusing on various form of "brain exercises", CBT therapy and exercise therapy. Things that are not only proven to not work, but actually proven to harm people with ME/CFS (of which long covid patients make up a large amount).
      - thenerdhead 2y ago
        They fund and do a lot of work beyond the horrible choices for initial RCTs. This fall we should hopefully see actual pharmaceutical interventions and a plethora of research they’ve been publishing. The more important parts of their programs are the omics and tissue biopsy programs. May they hopefully turn the ship…
- wpasc 2y ago
  For what’s it’s worth, autoimmune drugs are amongst the highest grossing due to their cost. Rheumatoid arthritis, psoriasis, MS all do have a lot of study. I wouldn’t say it’s enough, but I don’t think the prevalence of me/cfs alters anything due to the high prevalence of the other diseases. Immune disorders are definitely mysterious though
PaulKeeble 2y ago
Maybe but the immune dysfunction goes further in ME/CFS its not just a problem of reduced CD4 and heightened CD8 (which are the two cell types they seem to be talking about) its a wider set of oddities that seem related to exhausted cells with not enough energy stuck in "there is infection near by" operation mode. It might help reduce symptoms that are caused by the imbalance so it would certainly be worth a trial when they work out the details.
- trhway 2y ago
  >stuck in "there is infection near by" operation mode There are bunch of articles on successful treatment of CFS with methotrexate (which causes B-cells depletion whereis original CFS was associated in particular with B-cells over-presence after say viral infections/etc.)
avgDev 2y ago
I've encountered an individual who had fibro, me/cfs, pots diagnosis. Turns out his small nerve fibers were fried by an antibiotic. His skin punch biopsy showed reduced fibers. This may not be the case in everyone, but SFN is extremely under diagnosed. He was a chemist, and he ended up healing all his symptoms with pirenzepine. If I recall correctly they did the skin punch biopsy again and his physician was stunned when they saw regrowth of the fibers. Today, WinSanTor is in stage 3 trials with their drug. They designed a cream with main ingredient being pirenzepine. They are targeting diabetes but the med appears to work for small nerve fibers as well. Small nerve fibers control so much that any time people have weird unexplained symptoms it should be explored.
- carynh 2y ago
  > He was a chemist, and he ended up healing all his symptoms with pirenzepine. As in taking it orally for his SFN? That sounds equally fascinating as it sounds unlikely to me so I'd def love to read a bit more about it!
  - sharpshadow 2y ago
    Indeed Pirenzepine[1] is a muscarinic receptor antagonists. “The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the nervous system, and muscarinic receptor antagonists work to prevent this transmission from occurring.“[2] I could imagine that a let’s say relaxed nervous system recovers better. 1. https://en.m.wikipedia.org/wiki/Pirenzepine https://en.m.wikipedia.org/wiki/Pirenzepine 2. https://en.m.wikipedia.org/wiki/Muscarinic_receptor_antagonists https://en.m.wikipedia.org/wiki/Muscarinic_receptor_antagoni...
  - avgDev 2y ago
    Yes, he did take an oral dose, I believe it was higher than recommended dose, so some risk involved. I don't really see any studies on oral administration, but the new cream showed systemic relief.
treprinum 2y ago
Isn't thiamine tissue deficiency at the bottom of dysautonomia? Potentially leading to Alzheimer, MS, ALS over long periods of time if untreated depending on one's genetics and the way their body tries to adapt to it? I understand nobody tracks this over 30 years though. I think it's low-risk to try to address long-term tissue B1/B2/B3 deficiencies first and see if it helps. "The initial symptoms of thiamine deficiency beriberi are those of dysautonomia [1], a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome (POTS), inappropriate sinus tachycardia (IST), vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic syncope (NCS), neurally mediated hypotension (NMH), autonomic instability and a number of lesser-known disorders such as cerebral salt-wasting syndrome. Dysautonomia is associated with Lyme disease, primary biliary cirrhosis, multiple system atrophy (Shy–Drager syndrome) Ehlers–Danlos syndrome and Marfan syndrome for reasons that are not fully understood [2]. It has been hypothesized that the association of dysautonomia with so many different diagnoses is because a common form of dysautonomia originates from high calorie malnutrition. This leads to loss of oxidative efficiency (pseudo hypoxia) and subsequent disorganization of ANS controls that are mediated through the limbic system and brainstem."
- heartrending 2y ago
  Yes for some cases and any doctor who knows anything about dysautonomia tests and treats for it. It’s not root cause for many though because dysautonomia is a syndrome with potentially hundreds of reasons with the biggest being post-viral (autoimmune hypothesis) and EDS (vein elasticity hypotheis).
thenerdhead 2y ago
Very likely. All of these illnesses are diseases of the cells. We're entering the golden age of immune cell science. You figure out what immune cells are causing disease and how to restore them. Here the T cells are imbalanced and a specific protein is found to regulate the imbalance but the interferon is countering the protein's effects. Now you can target that in many ways and run all sorts of clinical trials.
- eszed 2y ago
  It seems to me that as we've gone layers deeper into organic processes we've repeatedly recapitulated Galenic theory: "rebalancing" more and more precisely-targeted "humours". Not saying this is bad - in fact, quite the contrary: it seems like a necessary stage on the way to more-sophisticated mechanitistic understanding.

It has been my hope that the number of me/cfs cases would finally drive enough research into autoimmune disorders in general, that we might finally figure it out. It seems very poorly understood from an outside perspective.

PaulKeeble 2y ago
There is no funding and since Long Covid appeared the funding for ME/CFS has completely vanished. If Long Covid ME like illness is the same then ME/CFS is getting lots of research right now, on the other hand if they turn out to be different ME/CFS patients are getting completely ignored.
- thenerdhead 2y ago
  Many ME experts are doing both. RECOVER is considering adding ME/CFS arms to its huge clinical trial platform. UCSF just added ME/CFS as a priority in their LIINC program. SARS-CoV-2 therapeutics won’t work on both but immune cell based ones may given they haven’t been tested in either yet. Both suggest a root cause of persistent viral antigen. Time will tell what works here.
  - Elinvynia 2y ago
    RECOVER is the biggest scam when it comes to research unfortunately. 90% of their studies are focusing on various form of "brain exercises", CBT therapy and exercise therapy. Things that are not only proven to not work, but actually proven to harm people with ME/CFS (of which long covid patients make up a large amount).
    - thenerdhead 2y ago
      They fund and do a lot of work beyond the horrible choices for initial RCTs. This fall we should hopefully see actual pharmaceutical interventions and a plethora of research they’ve been publishing. The more important parts of their programs are the omics and tissue biopsy programs. May they hopefully turn the ship…
wpasc 2y ago
For what’s it’s worth, autoimmune drugs are amongst the highest grossing due to their cost. Rheumatoid arthritis, psoriasis, MS all do have a lot of study. I wouldn’t say it’s enough, but I don’t think the prevalence of me/cfs alters anything due to the high prevalence of the other diseases. Immune disorders are definitely mysterious though

PaulKeeble 2y ago

Maybe but the immune dysfunction goes further in ME/CFS its not just a problem of reduced CD4 and heightened CD8 (which are the two cell types they seem to be talking about) its a wider set of oddities that seem related to exhausted cells with not enough energy stuck in "there is infection near by" operation mode. It might help reduce symptoms that are caused by the imbalance so it would certainly be worth a trial when they work out the details.

trhway 2y ago
>stuck in "there is infection near by" operation mode There are bunch of articles on successful treatment of CFS with methotrexate (which causes B-cells depletion whereis original CFS was associated in particular with B-cells over-presence after say viral infections/etc.)

avgDev 2y ago

I've encountered an individual who had fibro, me/cfs, pots diagnosis. Turns out his small nerve fibers were fried by an antibiotic. His skin punch biopsy showed reduced fibers. This may not be the case in everyone, but SFN is extremely under diagnosed. He was a chemist, and he ended up healing all his symptoms with pirenzepine. If I recall correctly they did the skin punch biopsy again and his physician was stunned when they saw regrowth of the fibers. Today, WinSanTor is in stage 3 trials with their drug. They designed a cream with main ingredient being pirenzepine. They are targeting diabetes but the med appears to work for small nerve fibers as well. Small nerve fibers control so much that any time people have weird unexplained symptoms it should be explored.

carynh 2y ago
> He was a chemist, and he ended up healing all his symptoms with pirenzepine. As in taking it orally for his SFN? That sounds equally fascinating as it sounds unlikely to me so I'd def love to read a bit more about it!
- sharpshadow 2y ago
  Indeed Pirenzepine[1] is a muscarinic receptor antagonists. “The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the nervous system, and muscarinic receptor antagonists work to prevent this transmission from occurring.“[2] I could imagine that a let’s say relaxed nervous system recovers better. 1. https://en.m.wikipedia.org/wiki/Pirenzepine https://en.m.wikipedia.org/wiki/Pirenzepine 2. https://en.m.wikipedia.org/wiki/Muscarinic_receptor_antagonists https://en.m.wikipedia.org/wiki/Muscarinic_receptor_antagoni...
- avgDev 2y ago
  Yes, he did take an oral dose, I believe it was higher than recommended dose, so some risk involved. I don't really see any studies on oral administration, but the new cream showed systemic relief.

treprinum 2y ago

Isn't thiamine tissue deficiency at the bottom of dysautonomia? Potentially leading to Alzheimer, MS, ALS over long periods of time if untreated depending on one's genetics and the way their body tries to adapt to it? I understand nobody tracks this over 30 years though. I think it's low-risk to try to address long-term tissue B1/B2/B3 deficiencies first and see if it helps. "The initial symptoms of thiamine deficiency beriberi are those of dysautonomia [1], a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome (POTS), inappropriate sinus tachycardia (IST), vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic syncope (NCS), neurally mediated hypotension (NMH), autonomic instability and a number of lesser-known disorders such as cerebral salt-wasting syndrome. Dysautonomia is associated with Lyme disease, primary biliary cirrhosis, multiple system atrophy (Shy–Drager syndrome) Ehlers–Danlos syndrome and Marfan syndrome for reasons that are not fully understood [2]. It has been hypothesized that the association of dysautonomia with so many different diagnoses is because a common form of dysautonomia originates from high calorie malnutrition. This leads to loss of oxidative efficiency (pseudo hypoxia) and subsequent disorganization of ANS controls that are mediated through the limbic system and brainstem."

heartrending 2y ago
Yes for some cases and any doctor who knows anything about dysautonomia tests and treats for it. It’s not root cause for many though because dysautonomia is a syndrome with potentially hundreds of reasons with the biggest being post-viral (autoimmune hypothesis) and EDS (vein elasticity hypotheis).

thenerdhead 2y ago

Very likely. All of these illnesses are diseases of the cells. We're entering the golden age of immune cell science. You figure out what immune cells are causing disease and how to restore them. Here the T cells are imbalanced and a specific protein is found to regulate the imbalance but the interferon is countering the protein's effects. Now you can target that in many ways and run all sorts of clinical trials.

eszed 2y ago
It seems to me that as we've gone layers deeper into organic processes we've repeatedly recapitulated Galenic theory: "rebalancing" more and more precisely-targeted "humours". Not saying this is bad - in fact, quite the contrary: it seems like a necessary stage on the way to more-sophisticated mechanitistic understanding.