The Enterovirus Theory of Disease Etiology in ME/CFS: A Critical Review (O'Neal and Hanson, 2021)

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I expect that at least some of those who had been 'cured of ME' by antiviral treatments didn't actually have ME (since there's no test for it). They may have had non-standard viral infections that looked similar to ME.
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How could you possibly differentiate between those two groups of people without a definitive diagnostic test? As of today both of those groups of people have what we know of as CFS.
 

Wishful

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How could you possibly differentiate between those two groups of people without a definitive diagnostic test?
Exactly. Without the ability to identify who actually has ME, we can't tell whether a treatment actually worked on ME.

As of today both of those groups of people have what we know of as CFS.
Well yes, since we can't differentiate, the term 'CFS' (or ME or SEID) is a vague catchall, including a lot of people who have unrelated chronic fatigue-like symptoms. So, a treatment that works for someone who actually has an unusual form of EBV won't necessarily work for someone with what might be ME if we had a definitive biomarker for it.
 

Pyrrhus

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sometexan84

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Right, one reason the side effects were severe is because Type I interferon affects the whole body. But Type III (lambda) works at just the organ barriers (epitheliums), like intestine, lung, etc.

View attachment 43294

IFN Type III (Lambda) was only recently discovered.

I believe it's the absolute best shot at removing persistent Enterovirus infection.

This Type III interferon is a very potent antiviral against enterovirus, and the natural IFN III is pretty much how the body gets rid of the acute EV infection in the first place.

Problem is, those of us w/ persistent EV had (at some point) a weak enough intracellular immune response to allow EV to take hold, where it then cleaves the proteins in the infected cells in order to block the IFN III response. That's how it evades, it blocks IFN III because IFN III will destroy it.

This is the missing link in Dr. John Chia's interferon treatments for CFS. He used IFN alpha and beta. People got better, then at some point they relapsed because it never destroyed the virus entirely.

IFN Lambda however has possibly the best antiviral effect on enterovirus, it works exactly where the virus is, and there are way less side effects so you can use it for longer.
I left out something important in here, regarding Dr. Chia's interferon trials.

Cells have these receptors on their surface, like interferon receptors for example. Our body's interferon will pretty much only work on cells of the matching interferon receptor.

So, in Dr. Chia's experiments, he treated w/ synthetic Type I Interferons, alpha and beta. Alpha for example... for IFN alpha to aid in controlling infections, infected cells need to have a IFN-α receptor (IFNAR) on the cell's surface, so interferon can bind to it.

That's fine... because receptors for alpha and beta interferons are found in many different cell types in the body.

However, in the intestinal epithelium, the reservoir for Enterovirus, things are different. Here, the intestinal epithelial cells (IECs) mostly have the Type III interferon lambda receptor, and NOT Type I interferon receptors.

This means that in Dr. Chia's experiments, it's likely that the Type I IFN treatments successfully treated infected cells throughout the body, resulting in loss of symptoms. And that the infected IECs were NOT successfully treated (due to different IFN receptors), resulting much later in relapse.

Hence IFN Lambda being the missing link I was talking about earlier, which works at the epithelial barriers (where the majority of cells use this Lambda receptor) of the body instead of the whole body. And now we know why that is.
 

Hip

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However, in the intestinal epithelium, the reservoir for Enterovirus, things are different. Here, the intestinal epithelial cells (IECs) mostly have the Type III interferon lambda receptor, and NOT Type I interferon receptors.
Did you find a paper indicating that the epithelial cells have much higher levels of type III receptors, compared to type I receptors? If so, that could make interferon lambda interesting.


Apparently cyclosporin A and alisporivir are drugs which induce interferon lambda. Ref: here

But for acute coxsackievirus B infections, cyclosporin seems to make the infection worse, in mice. Ref: here

Of course for chronic non-cytolytic coxsackievirus B, cyclosporin may have different effects.


I did just now find a paper indicating that interferon lambda may have pathological effects, in the context of systemic autoimmune diseases:
However, evidence now suggests that type III interferons have complex effects on both innate and adaptive immune responses and might also be pathogenic in systemic autoimmune diseases.
Ref: here

Whether that only applies to endogenous interferon lambda, or whether it also applies to exogenous interferon lambda therapy, I am not sure.
 

sometexan84

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Did you find a paper indicating that the epithelial cells have much higher levels of type III receptors, compared to type I receptors? If so, that could make interferon lambda interesting.


Apparently cyclosporin A and alisporivir are drugs which induce interferon lambda. Ref: here

But for acute coxsackievirus B infections, cyclosporin seems to make the infection worse, in mice. Ref: here

Of course for chronic non-cytolytic coxsackievirus B, cyclosporin may have different effects.


I did just now find a paper indicating that interferon lambda may have pathological effects, in the context of systemic autoimmune diseases:

Ref: here

Whether that only applies to endogenous interferon lambda, or whether it also applies to exogenous interferon lambda therapy, I am not sure.
Yes, you can google it and find a bunch of references showing Type III IFN in epithelial cells.

I've seen that article as well, I'm not too concerned. Peginterferon Lambda has actually been used so much on humans. It's safe.
 

sometexan84

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New Lambda Drug!

PEGINF-L Chimera (PSP001) - Interferon Lambda Chimera
from Prosit Sole Biotechnology in Beijing


Prosit Sole Biotechnology Initiates First-In-Human Clinical Trial of Novel Interferon Lambda Chimera in US

Prosit Sole Biotechnology, a clinical-stage biotech company developing novel protein therapeutics, today announces that it has initiated the first-in-human ("FIH") Phase I clinical trial of PSP001 in US. PSP001 is a novel, long acting and potent interferon lambda chimera injection. The first dose was administered on May 25, 2021
Might even be better than Peginterferon Lambda (from Eiger) because it's IFN lambda 1-3.... not just 1

Anyone know chinese?
http://www.prositsole.com/index.php?catid=27(edited)
1628374468098.png


Should I start a new PR thread for this?
 

Hip

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Anyone know chinese?
You can use the camera on the Google Translate smartphone app to translate images like this. It's handy for translating the info on boxes of drugs from foreign countries too.

Here is the translation of the above image:

Indications

PSP001 Chronic norovirus in immunocompromised population
Viral asthma immune
Cytomegalovirus

PSPO02 Minimally invasive repair surgery for cartilage injury

PSP006 Fetal/neonatal heteroimmune thrombocytopenia

PSP007 Phenylalanine mutant phenylketonuria

—————————————————————

PSP101 Severe clinical emergency rare diseases

PSP102 Severe clinical emergency rare diseases

Did they provide any idea when this interferon lambda product is going to hit the market? Looks like it is still in early phase clinical trials. So it might be another 5 years or so I guess.
 

sometexan84

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You can use the camera on the Google Translate smartphone app to translate images like this. It's handy for translating the info on boxes of drugs from foreign countries too.
How did I not know this :headslap:

Did they provide any idea when this interferon lambda product is going to hit the market? Looks like it is still in early phase clinical trials. So it might be another 5 years or so I guess.
Based on the pipeline chart, it looks to be ready next yr
 

Hip

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I've seen that article as well, I'm not too concerned. Peginterferon Lambda has actually been used so much on humans. It's safe.
I would think interferon lambda is going to be safe; but people with a systemic autoimmune disease (like lupus, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, psoriasis or Sjogren's for example) might want to approach with caution.
 

sometexan84

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can you find a CAS NUMBER to identify the PSP001 etc? This way we could inquire at manufacturers. Maybe this chinese version is more widely available in chinese productions!
Actually, that CAS number I'd found before I think is for a different "PSP001"... and I can find nothing else on the relevant PSP001, so it almost seems kind of shady
 

Pyrrhus

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The author Maureen Hanson has now written an editorial describing this paper:

Are enteroviruses behind mysterious outbreaks of chronic fatigue syndrome?
https://blog.frontiersin.org/2021/0...me-viruses-maureen-hanson-cornell-university/
(Hanson has already expressed regret at the editor's choice of photo to accompany her editorial.)

Excerpt:
Maureen Hanson said:
Prof Maureen Hanson of Cornell University discusses how she and graduate student James O’Neal searched through the research archives to see whether a genus of RNA viruses called enteroviruses are the most likely culprits and whether the findings have implications in future ‘long Covid’ research.