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

[ChookityPop]

what is the best test for enterovirus? And is there a lab somewhere in europe that does it?

Is there anyway to try IFN Lambda now?

 

[Martin aka paused||M.E.]

Hip has a road map where it’s mentioned. For antibodies it’s the neutralization test (only a few labs offer it, in Germany IMD Berlin)
In case you want to have a full enterovirus panel you need a PCR taken from a tissue sample (Dr. Chia uses stomach biopsies)
https://mecfsroadmap.altervista.org/#coxsackievirus-b-and-echovirus

 

[Hip]

But it's indeed interesting that they reach the exact same level. As if the former infected cells had a marker and the none infected cells don't

Yeah, it's strange. Maybe viral RNA levels in each cell which is infected go down a lot during interferon therapy, but the RNA is not quite fully cleared from the cell, so then the viral RNA regrows back in the same cells once interferon therapy is over.


I's just frustrating that interferon therapy works so well for many enterovirus ME/CFS patients (approx 50% respond to interferon), but does not seem to permanently clear the virus, so patients relapse typically 4 to 14 months later (usually after a bout of heavy exertion, like going on a hiking vacation — that's how Chia's son relapsed from his interferon therapy).


By contrast, interferon therapy for chronic hepatitis C virus infection of the liver sometimes leads to complete eradication of the hep C virus. So it can cure hep C. Although I believe they give interferon for a longer period to hep C patients, like 12 months. Whereas in ME/CFS studies and in Chia's experiments, I think it was more like 3 months.

Maybe if ME/CFS patients took interferon for a year, it might lead to eradication of enterovirus. Though you generally feel terrible during interferon therapy, so taking it for a year would be some commitment.



An alternative idea I had that might prevent the ME/CFS relapse that occurs after interferon therapy is taking low-dose interferon forevermore, once regular interferon therapy has placed you in remission or near remission.

Normally you cannot take interferon by injection indefinitely, as even with low-dose interferon, your body eventually starts making anti-interferon antibodies, which unfortunately then disable the injected interferon.

But if you take low-dose interferon by a suppository rather than injection, these antibodies do not appear. So I was thinking that a low-dose interferon suppository maintenance dose taken indefintely could prevent relapse after the normal 3 month course of interferon therapy to treat ME/CFS. More info on interferon suppositories in this post.

 

[Martin aka paused||M.E.]

Yeah, it's strange. Maybe viral RNA levels in each cell which is infected go down a lot during interferon therapy, but the RNA is not quite fully cleared from the cell, so then the viral RNA regrows back in the same cells once interferon therapy is over.


I's just frustrating that interferon therapy works so well for many enterovirus ME/CFS patients (approx 50% respond to interferon), but does not seem to permanently clear the virus, so patients relapse typically 4 to 14 months later (usually after a bout of heavy exertion, like going on a hiking vacation — that's how Chia's son relapsed from his interferon therapy).


By contrast, interferon therapy for chronic hepatitis C virus infection of the liver sometimes leads to complete eradication of the hep C virus. So it can cure hep C. Although I believe they give interferon for a longer period to hep C patients, like 12 months. Whereas in ME/CFS studies and in Chia's experiments, I think it was more like 3 months.

Maybe if ME/CFS patients took interferon for a year, it might lead to eradication of enterovirus. Though you generally feel terrible during interferon therapy, so taking it for a year would be some commitment.



An alternative idea I had that might prevent the ME/CFS relapse that occurs after interferon therapy is taking low-dose interferon forevermore, once regular interferon therapy has placed you in remission or near remission.

Normally you cannot take interferon by injection indefinitely, as even with low-dose interferon, your body eventually starts making anti-interferon antibodies, which unfortunately then disable the injected interferon.

But if you take low-dose interferon by a suppository rather than injection, these antibodies do not appear. So I was thinking that a low-dose interferon suppository maintenance dose taken indefintely could prevent relapse after the normal 3 month course of interferon therapy to treat ME/CFS. More info on interferon suppositories in this post.

Question is if low dose treatments would be enough to eridate the virus and not only block replication

 

[Hip]

Question is if low dose treatments would be enough to eridate the virus and not only block replication

I would doubt that low-dose interferon could eradicate enterovirus from ME/CFS patients.

But if you substantially reduced the enterovirus infection with a course of injectable interferon (like Dr Chia sometimes uses), and this puts you in near remission, I wonder if taking daily interferon suppositories would prevent relapse back into ME/CFS, and thus help maintain the gains you made during the course of injectable interferon.

Interferon suppositories bought from Russian online prescription-free pharmacies are inexpensive.

 

[Martin aka paused||M.E.]

I would doubt that low-dose interferon could eradicate enterovirus from ME/CFS patients.

But if you substantially reduced the enterovirus infection with a course of injectable interferon (like Dr Chia sometimes uses), and this puts you in near remission, I wonder if taking daily interferon suppositories would prevent relapse back into ME/CFS, and thus help maintain the gains you made during the course of injectable interferon.

Interferon suppositories bought from Russian online prescription-free pharmacies are inexpensive.

Yes ok, would be interesting to know. Perhaps with adequate pacing possible.
Online pharmacies from foreign countries and Germany... Bad luck for me

 

[Pyrrhus]

By contrast, interferon therapy for chronic hepatitis C virus infection of the liver sometimes leads to complete eradication of the hep C virus.

That is an extraordinarily rare outcome- perhaps 1% of patients.

Even when Interferon is combined with Ribavirin for 12 months, it only works 50% of the time, with sometimes horrendous side effects.

 

[Hip]

That is an extraordinarily rare outcome- perhaps 1% of patients.

Just did some Googling on this, and found an article which says:

Interferon injections had a cure rate of about 40 to 50 percent.

Newer pill treatments have cure rates of nearly 100 percent. In clinical trials, Harvoni, for example, achieved a cure rate of about 94 percent after 12 weeks. Other drugs and combination medications had similarly high cure rates in that same time frame.

Of course nowadays we have these new hepatitis C virus antiviral drugs like Harvoni (= sofosbuvir + ledipasvir) which work much better than interferon, and unlike interferon do not make patients feel ghastly while taking them.

A few years ago it was really hoped that sofosbuvir might also work for enteroviruses, but Dr De Palma in Belgium showed that sadly sofosbuvir had no antiviral effects for enterovirus (see this post).


It is unfair that drug companies invest in antiviral drugs to treat hepatitis C virus, but do very little research on treating enteroviruses like coxsackievirus B, which are linked not only to ME/CFS, but also type 1 diabetes, the heart disease called dilated cardiomyopathy, heart valve disease, amyotrophic lateral sclerosis (a motor neuron disease), Sjögren's syndrome, Crohn's disease, and more recently were linked to Parkinson's also.

 

[Pyrrhus]

Just did some Googling on this, and found an article which says:

That article quotes an FDA release, which was apparently referring to the combination of Interferon with Ribavirin, although the FDA article did not make that clear as it should have.

 

[Hip]

That article quotes an FDA release, which was apparently referring to the combination of Interferon with Ribavirin, although the FDA article did not make that clear as it should have.

That's interesting, as Dr Chia also tried interferon + ribavirin for ME/CFS, giving this to patients for 2 to 6 months. See his paper here.

I understand that for hep C, treatment is typically 6 to 12 months. Which makes you wonder whether treating ME/CFS patients for 12 months with this combo therapy might also lead to full elimination of enterovirus in a percentage of patients.

 

[Pyrrhus]

Unfortunately, Ribavirin is the type of direct-acting antiviral (DAA) called a mutagenic nucleoside analogue, which requires very high doses to suppress the virus.

At these high doses, Ribavirin causes bone marrow suppression, which limits its practical use.

 

[sometexan84]

Yeah, it's strange. Maybe viral RNA levels in each cell which is infected go down a lot during interferon therapy, but the RNA is not quite fully cleared from the cell, so then the viral RNA regrows back in the same cells once interferon therapy is over.

I think this may be the case.

The GI tract is generally the initial site of infection, where it has a great affinity towards the epithelial cells. Let's say this is its base of operations. And maybe it later spreads to other areas of the body. That could likely be the case in the Chia studies, since they were all very severe, suggesting more widespread viral infection.

So, maybe the IFN alpha actually got rid of infected cells throughout various places in the body. But it wasn't enough to take down the base of operations, so when the virus recovered, it spread to the same places it did before, using the same means.

IFN alpha can't take down RNA enteric viruses on its own, not in the epithelial cells of the small intestine.

Article from 2011, shows Type I IFN (IFN alpha, beta, etc) is not enough to compensate for lack of Type III IFN (lambda) in rotavirus infection in gastrointestinal tract.

IFN-λ determines the intestinal epithelial antiviral host defense

I think both interferon types actually have great antiviral activity to enterovirus in the gut. But it appears to be a difference in IFN signaling specifically in the GI tract, which makes IFN lambda so important in the epethiliums.

 

[Hip]

IFN alpha can't take down RNA enteric viruses on its own, not in the epithelial cells of the small intestine.

Article from 2011, shows Type I IFN (IFN alpha, beta, etc) is not enough to compensate for lack of Type III IFN (lambda) in rotavirus infection in gastrointestinal tract.

IFN-λ determines the intestinal epithelial antiviral host defense

That's interesting. So maybe one of these interferon combo treatments would work best, like say interferon beta + interferon lambda.



The first time I became aware of this newly-discovered interferon lambda was via this paper, which says that coxsackievirus B specifically blocks interferon lambda release, by blocking TLR3 and MDA5/RIG-I.

 

[sometexan84]

That's interesting. So maybe one of these interferon combo treatments would work best, like say interferon beta + interferon lambda.

I was thinking of a combo treatment w/ lambda as well. alpha or beta. or w/ something else like the ribivarin.

Btw, this might also be why IFN works w/ Hep C in the liver and not Enterovirus in the gut. Seems IFN lambda is less important in many areas, where IFN alpha has less of an impact specifically in the GI tract. Maybe that's the case in the liver as well.

 

[sometexan84]

The first time I became aware of this newly-discovered interferon lambda was via this paper, which says that coxsackievirus B specifically blocks interferon lambda release, by blocking TLR3 and MDA5/RIG-I.

Yea, that's the same group of Swedes that did this 2021 article

Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection?

I've gone over it a ton, learned a lot.

 

[sometexan84]

If only someone could show Dr. Chia the latest on IFN lambda and its potential for treating persistent enterovirus in CFS, he may be convinced to ask Eiger Pharmaceuticals for a small trial on their Pegylated Interferon Lambda. Plus it's in Phase III, they don't have much to lose from a small trial like that. It's all about convincing the one research scientist that might be interested.

 

[ChookityPop]

If only someone could show Dr. Chia the latest on IFN lambda and its potential for treating persistent enterovirus in CFS, he may be convinced to ask Eiger Pharmaceuticals for a small trial on their Pegylated Interferon Lambda. Plus it's in Phase III, they don't have much to lose from a small trial like that. It's all about convincing the one research scientist that might be interested.

What about getting lots of people to send the info to his email or something and hope for the best?

 

[ChookityPop]

Yeah, it's strange. Maybe viral RNA levels in each cell which is infected go down a lot during interferon therapy, but the RNA is not quite fully cleared from the cell, so then the viral RNA regrows back in the same cells once interferon therapy is over.


I's just frustrating that interferon therapy works so well for many enterovirus ME/CFS patients (approx 50% respond to interferon), but does not seem to permanently clear the virus, so patients relapse typically 4 to 14 months later (usually after a bout of heavy exertion, like going on a hiking vacation — that's how Chia's son relapsed from his interferon therapy).


By contrast, interferon therapy for chronic hepatitis C virus infection of the liver sometimes leads to complete eradication of the hep C virus. So it can cure hep C. Although I believe they give interferon for a longer period to hep C patients, like 12 months. Whereas in ME/CFS studies and in Chia's experiments, I think it was more like 3 months.

Maybe if ME/CFS patients took interferon for a year, it might lead to eradication of enterovirus. Though you generally feel terrible during interferon therapy, so taking it for a year would be some commitment.



An alternative idea I had that might prevent the ME/CFS relapse that occurs after interferon therapy is taking low-dose interferon forevermore, once regular interferon therapy has placed you in remission or near remission.

Normally you cannot take interferon by injection indefinitely, as even with low-dose interferon, your body eventually starts making anti-interferon antibodies, which unfortunately then disable the injected interferon.

But if you take low-dose interferon by a suppository rather than injection, these antibodies do not appear. So I was thinking that a low-dose interferon suppository maintenance dose taken indefintely could prevent relapse after the normal 3 month course of interferon therapy to treat ME/CFS. More info on interferon suppositories in this post.

How low dose are we talking? And what would it cost ish do you think?

 

[Hip]

How low dose are we talking? And what would it cost ish do you think?

Russian interferon suppositories are typically sold in doses of 150,000 IU, 1 million IU, and 3 million IU.

A packet of 10 x 1 million IU suppositories costs around $50. So that's $5 for 1 million IU.


It's anyone guess what might be the appropriate interferon maintenance dose to prevent regrowth of an enterovirus infection after a course of injectable interferon.

But this study on low-dose rectal interferon suppositories to treat hepatitis C virus found that even a dose as low as 1000 IU daily measurably suppressed viral replication.

Thus one could consider doses of say 125,000 IU daily, just as a guess, because that would be reasonably economical for long-term use. Suppositories are made of a soft waxy substance, and can be easily cut with a knife. So one could cut a 1 million IU suppository into say 8 pieces of 125,000 IU. Then each piece would cost around $0.62.


More info in doses and pharmacies which sell Russian interferon suppositories in this post.

Note that Dr Chia finds interferon does not work for CVB4, but does work for other Coxsackie B viruses.

 

[sometexan84]

Speaking to the Dr. Chia IFN studies, the patient titers returning to pre-treatment levels, etc... I found the chart that shows the titer levels during and after treatment.

I highlighted some stuff in red for an example, to try and make it a little easier to understand...

And here's the actual charts for patients, most of which show the Interferon + Ribavirin treatment.

So, a couple of things I noticed. I had forgotten that the antibody titers are maxed out at >=1:640. So we have no idea of knowing if the patients titers actually returned to their pre-treatment level.

Since most of them started at >=1:640, for all we know their actual levels were like 1:10,000 or something. And maybe when they relapsed their numbers went to 1:1,280 or something... who knows.

Also, just looking at the patients graphs, it actually does not look like titers jumped all the way back up to pre-treatment levels. Though, hard to say cause who knows what happened after 24 months.

Patient B... Titers of 1:20 !!!

On a different note, you can see treatment dropped this patients titers all the way down to 1:20 (at least that's what the titer looks like to me). And they still end up going way back up.

This implies 1:20 does not mean you're out of the woods.