Strikingly Positive' Effect of Novel MS Agent. Has anyone tried it on ME/CFS?

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Woodyrob

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Not currently for ME/CFS but I have a hunch it will be helpful.

I’ve been seeing more overlaps between MS and ME more lately. As a certain percentage of ME/CFS patients develop MS and probably vice versa. So I wonder if this drug could also work on ME?. As its target seems to be further upstream, prior to B and T-cell activation. Possibly making the downstream effect more broad? Also the innate immune system is of interest in ME/CFS, something this drug targets

Plus it doesn’t seem to reduce overall immunity too which is good.

Except: “…frexalimab would be unique as a novel second-generation monoclonal antibody designed to block the costimulatory CD40/CD40L cellular pathway.
Importantly, the mechanism is believed to potentially modify T- and B-cell activation and innate immune cell function, for an effect of reducing inflammation without depleting B cells”.


'Strikingly Positive' Effect of Novel MS Agent-MedScape
https://www.medscape.com/viewarticle/993011


If a drug like that found its way into our hands, I wouldn’t blink twice at jabbing it in me as an experiment. Sometimes we have to break a fingernail to get the job done. lol
 
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Anish04

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Cfs is not mentioned in article. How you can assume that if one thing works great for MS will also work for CFS? Edited as original comment was a bit offensive. Do you think any possible mechanism behind it working for CFS?
 
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Anish04

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cfs since 1998 said:
He's not assuming, he's speculating.


MS patients aren't even cured by MS drugs.
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Ms and cfs aren't very closely related. As someone said ron once mentioned only 25% of cases are related. Also if MS drugs don't work for MS itself can you explain any possible mechanism by which it can help cfs?

(I am not offending just asking if there's any mechanism behind it which you and OP think)
 
cfs since 1998

cfs since 1998

Senior Member
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Anish04 said:
Ms and cfs aren't very closely related. As someone said ron once mentioned only 25% of cases are related.
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25% is significant when both illnesses are relatively rare, <1% of the population. They have numerous symptoms in common. They are both immune-mediated. Both exhibit neuroinflammation. Autoantibodies have been found in ME/CFS patients, giving rise to the hypothesis that it's an autoimmune disease. (If we had the money that MS had, maybe it would be more than a hypothesis by now.) The female to male ratios in MS and ME/CFS are almost identical. Both have been linked to Epstein-Barr Virus. Both are more common at high latitudes.

Also if MS drugs don't work for MS itself can you explain any possible mechanism by which it can help cfs?
Click to expand...
Presumably modulation of the immune system, but there are a lot of drugs used for various diseases where we don't know the mechanism.
 
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Woodyrob

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Anish04 said:
Ms and cfs aren't very closely related. As someone said ron once mentioned only 25% of cases are related. Also if MS drugs don't work for MS itself can you explain any possible mechanism by which it can help cfs?

(I am not offending just asking if there's any mechanism behind it which you and OP think)
Click to expand...
Assuming that ME/CFS is an autoimmune disease (I’m confidently assuming it is) and knowing there’s an MS ME/CFS overlap…

I’m hoping because of the upstream effect of this drug affecting functions downstream, I’m wondering if it is tackling something fundamental in autoimmunity in general. as it seems like the drug is preventing the cascade effect of that maybe broader downstream. i.e. downstream are instructions from the immune system to making mistakes known as Molecular Mimicry (a learnt mistake to attack a person’s own body.

Maybe this drug is helping the body properly identify what antigens are foreign or friendly. The immune system in healthy people normally turns on autoimmunity temporarily during an infection and off again afterwards. It’s just unlucky people that end up with MS, rheumatoid, arthritis, lupus, etc where theirs is stuck on permanently.

I winder if molecular mimicry is what’s happening in many cases of ME/CFS. In fact, there was a Swedish study that found an a sub Group of ME/CFS patients had auto antibodies to the beta2 adrenergic, the muscarinic M2 receptors. Maybe other subgroups have auto antibodies to other receptors that are essential for energy production etc.

Also important to know that’s there are actual bodily functions that turn off and on systems by using autoantibodies as the switch. Most of us believe there’s a switch in us that hasn’t turned off after it turned on in our original infection. (think Robert Naviaux’s ‘Cell Danger Response’ CDR) that puts us into a sickly unwell state until the body recovers. Unfortunately like MS patients ME/CFS patients don’t recover, and Naviaux believes ME/CFS patients are permanently stuck with CDR turned on.

I’m suggesting that CDR is possibly turned on and off via either autoantibodies, or possibly by the innate immune system that is turning on CDR but somehow not turning it off. (I see this drug also helps modify not just antibodies but T-cells and the innate immune system function)

The reason why I’m reasonably confident that MECFS is a likely to be an auto immune disease, is because when ME/CFS and Long Covid patients are questioned it’s often found that autoimmunity runs in their family history.

There’s 4 family members on my mother’s side with autoimmune diseases and one that was possibly MS.

Even ME/CFS runs in families.



Maybe this drug offers us hope too?
 
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Osaca

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Before this myth keeps on getting perpetuated Ron Davis didn't say something like "there is a relation in 25% of cases". What they found is that in a very small study, 1/4 of patients had some autoantibodies that can sometimes also be associated with MS (this is a very weak connection).

Other than that I agree with everything @cfs since 1998 says. Off all existing diseases (apart from other post-viral diseases) the one that based on current knowledge shares the most overlap and proposed pathways ideas with ME/CFS is MS.

Edit: To be precise it was said "Autoantibodies toward myelin basic protein are present in 25% of ME/CFS patients"
 
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Oliver3

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Pretty sure Ron said directly that he thinks that a quarter of m.e. patients have m.s. as well.
Remember listening to the talk. Could've misremembered it I guess
 
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Osaca

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Oliver3 said:
Pretty sure Ron said directly that he thinks that a quarter of m.e. patients have m.s. as well.
Remember listening to the talk. Could've misremembered it I guess
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I can only repeat exactly what I have already said above. Ron Davis has never said that 1/4 of ME/CFS patients have MS. What was said is that in an extremely small experiment (not even a study) 25% of ME/CFS patients had antibodies against Myelin basic protein. This is the reference www.youtube.com/watch?v=F6pOotJewb0 (from 9:30 onwards).

Those are 2 different things.
 
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Wishful

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While I agree that there doesn't seem to be any reason to believe that this drug is any more likely to work for ME than any other immunomodulator, I also agree with the OP's "give it a jab" philosophy. We don't have anything that works reliably, so any new drug that alters the immune system or specific steps in cell functions might as well be given a try unless there's a significant risk of harm. Imagine if you took a dose of this and it made your brainfog many times worse, and repeated testing proved that it was a reliable response. That would identify a specific pathway involved in that ME symptom, which could then be followed up on.

ME research funding is spread out along however many paths because so far there is no sign of a trail to follow. If the CD40/CD40L pathway was proven to be involved in ME (or even for just one symptom) it would allow researchers to focus on that. It's the difference between searching the wilderness for a specific but only vaguely defined animal, and having a clear set of tracks identified as belonging to that animal.

There's no evidence that this drug is worth a multi-million dollar study, but if someone wants to give it a try, I support that. If not for legal hassles, I think drug companies would be willing to provide free samples for people with untreatable diseases, since it could open up new markets.
 
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Oliver3

Senior Member
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Osaca said:
I can only repeat exactly what I have already said above. Ron Davis has never said that 1/4 of ME/CFS patients have MS. What was said is that in an extremely small experiment (not even a study) 25% of ME/CFS patients had antibodies against Myelin basic protein. This is the reference www.youtube.com/watch?v=F6pOotJewb0 (from 9:30 onwards).

Those are 2 different things.
Click to expand...
I'll take your word for it and rewatch everything
 
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hapl808

Senior Member
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Osaca said:
What was said is that in an extremely small experiment (not even a study) 25% of ME/CFS patients had antibodies against Myelin basic protein. This is the reference www.youtube.com/watch?v=F6pOotJewb0 (from 9:30 onwards).
Click to expand...

I have quite a few MS symptoms and the feeling that my immune system is attacking muscle or connective tissue or something. I've wondered if an atypical MS diagnosis would make sense, but before I could pursue it further I got more severe from all the encouragement for me to push through (which actually would've likely been contraindicated with MS). Maybe a moot point for me now.
 
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datadragon

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Multiple sclerosis is a disease in which the immune system attacks the myelin sheath, the protective covering of nerve cells causing communication problems between the brain and the rest of the body. MS is driven by immune cells attacking oligodendrocytes and the myelin they produce, which is an insulating layer ensheathing nerve cells. https://www.sciencedaily.com/releases/2022/01/220128141316.htm

In ME/CFS there is low confirmed butyrate and likely higher 4EPS. Butyrate suppresses demyelination and enhances remyelination and butyrate is also lower at the same time as a downstream effect of the gut dysbiosis. Butyrate may affect oligodendrocytes directly. Butyrate treatment facilitated the differentiation of immature oligodendrocytes and also is involved with autoimmunity. This research had mentioned that the 4EPS (4-ethylphenyl sulfate) metabolite, produced by bacteria that reside in the mouse gut, can travel to the brain and alter the function of brain oligodendrocytes cells which were altered. These cells are important in part because they produce a protein called myelin, which acts as a protective coating around neurons and nerve fibers called axons, like insulation around an electrical wire. The team found that in the presence of 4EPS, oligodendrocytes are less mature and consequently produce less myelin and also anxiety I mentioned previously here. https://forums.phoenixrising.me/threads/bc007-what-are-your-thoughts.87520/post-2442283

Another interesting research showed a biochemical pathway that dendritic cells use to stop other immune cells from attacking the body and this pathway can be activated with lactate. https://medicalxpress.com/news/2023-08-probiotic-multiple-sclerosis.html gut microbes can utilise lactate and convert it to propionate, butyrate or acetate. https://www.cambridge.org/core/jour...t-microbiome/70FFDA0D826775206007393EB4E21FE2 Oligodendrocytes can generate lactate, which can then be transferred to axons to generate metabolic energy in the form of ATP. Indeed, a number of glycolytic and Krebs cycle enzymes such as succinate dehydrogenase and fumarase are expressed in the myelin sheath, which contribute to glucose catabolism and ATP production https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912544/
 
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