ME/CFS International Research Symposium, March 2019, Australia

[Alvin]

As RD said, just because it makes the blood of pwME act normal, doesn't necessarily mean it has any practical application, but it's a good start. Lots of meds have side effects that make them have a therapeutical value beyond their intended use. My impression was that they don't know why it makes the blood act normal yet, for all we know it works as a sacrificial protein in pwME too. I really don't know, just thinking out loud

I understand, i didn't mean to sound like i was saying i don't believe him, what i meant was why does it work, if we can figure that out it might tell us something about ME that we don't know yet.

 

[Perrier]

I don't get why copaxone would work in ME. In MS as i understand it it provides something for the body to attack, essentially as a sacrificial protein. We don't have MS even if what we have might be in a related but differing family.

From some of my reading, there are MS doctors who are cautioning MS folks with regard to Copaxone, as it has nasty side effects. And the ME population is often a very sensitive one. Also, I might just add that at least 2 CFS doctors prescribed T3 (compounded) for my daughter. The result was slow but severe hair loss; and no elimination of PEM; a bit more energy--yes, but then a crash from hell, as they say. With the slight increase in energy a bit more movement was attempted, but the payback was utterly frightening and lengthy.

I am very distressed that these conferences are not resulting in anything very concrete, except for publications for the researchers which are important, and travel grants, and experiencing new places and fine weather. (In my professional life I went to tons of conferences, and delivered papers. So I know the drill. ) I would dearly love to be wrong. We still do not know what is causing this illness, and where specifically the problems reside (except for almost everywhere). There is something seriously wrong somewhere if a body gets PEM from trying to brush his/her teeth, or send one email from bed. What is causing this?? WE don't know, do we. Someone out there, please tell me I am wrong.

 

[mariovitali]

From some of my reading, there are MS doctors who are cautioning MS folks with regard to Copaxone, as it has nasty side effects. And the ME population is often a very sensitive one. Also, I might just add that at least 2 CFS doctors prescribed T3 (compounded) for my daughter. The result was slow but severe hair loss; and no elimination of PEM; a bit more energy--yes, but then a crash from hell, as they say. With the slight increase in energy a bit more movement was attempted, but the payback was utterly frightening and lengthy.

Yes we are still trying to identify what is going on even though we have some signals (impaired NK cells functioning, RBC deformability and others). The big question is where do all of these come from.

We also know that there is a lot of oxidative stress taking place in ME patients and -i hypothesise- that this is a very important aspect. Unfortunately, metabolism generates oxidative stress -there can be no metabolism without it- and so what it seems to me that is happening is that ME patients cannot tolerate that. It is like trying to put your foot on the pedal (=T3) on an engine that cannot handle higher speed. This will simply not work. I also wonder if hypothyroidism seen on ME patients is an action done on purpose from the body to minimise oxidative stress by bringing down metabolism (i dont know if this makes sense medically though).

 

[Alvin]

From some of my reading, there are MS doctors who are cautioning MS folks with regard to Copaxone, as it has nasty side effects. And the ME population is often a very sensitive one. Also, I might just add that at least 2 CFS doctors prescribed T3 (compounded) for my daughter. The result was slow but severe hair loss; and no elimination of PEM; a bit more energy--yes, but then a crash from hell, as they say. With the slight increase in energy a bit more movement was attempted, but the payback was utterly frightening and lengthy.

So from the sounds of it T3 is not an issue but its having a stimulant effect but that effect is causing the disease to respond badly.
Thats useful information saying don't use it. Very unfortunate that many had to suffer to bring us this knowledge

I am very distressed that these conferences are not resulting in anything very concrete, except for publications for the researchers which are important, and travel grants, and experiencing new places and fine weather. (In my professional life I went to tons of conferences, and delivered papers. So I know the drill. ) I would dearly love to be wrong. We still do not know what is causing this illness, and where specifically the problems reside (except for almost everywhere). There is something seriously wrong somewhere if a body gets PEM from trying to brush his/her teeth, or send one email from bed. What is causing this?? WE don't know, do we. Someone out there, please tell me I am wrong.

I agree, we need a disease mechanism or at least an understanding of what the symptoms are being caused by. I also want to know what PEM is and why we get worse with exercise or over time. For many years i was more or less able to function but how long till PEM kept dropping to where i could not work. Then my ability till PEM dropped greatly as well as the interval. Plus the cognitive issues, wtf is causing them.
My impression is that we are where we should have been 30 years ago, if we get loads of funding today we could try to catch up in the next 5-10 years, but yous simply can't fully undo harms from the past.
I want to know the identity of the molecule causing the signal in Dr Davis nanoneedle, if w knew what it was it might help us identify the source and that may lead to a treatment or even cure. Then again it might be an incidental or even incorrect finding. We don't know till we try.

 

[Sunshine3]

The Norwegians have also noted something in the blood. Mark Davis is surely looking for it. I only saw one video clip from Ron Davis but I thought he seemed optimistic, more alive and upbeat than usual. He presented very well. He is on no holiday, he is on a mission. I think Phair equally wants to find answers asap. Waiting is hard but we are moving.

Ron Davis said at one point this is one of the worst diseases you could possibly have. That meant so much to me.

 

[mariovitali]

The Norwegians have also noted something in the blood. Mark Davis is surely looking for it. I only saw one video clip from Ron Davis but I thought he seemed optimistic, more alive and upbeat than usual. He presented very well. He is on no holiday, he is on a mission. I think Phair equally wants to find answers asap. Waiting is hard but we are moving.

Ron Davis said at one point this is one of the worst diseases you could possibly have. That meant so much to me.

I cannot recall where i read it but Phair is looking for a metabolic trap in Tyrosine metabolism. Something that could be very important, i really look forward to what they find on this one.

 

[Perrier]

The Norwegians have also noted something in the blood. Mark Davis is surely looking for it. I only saw one video clip from Ron Davis but I thought he seemed optimistic, more alive and upbeat than usual. He presented very well. He is on no holiday, he is on a mission. I think Phair equally wants to find answers asap. Waiting is hard but we are moving.

Ron Davis said at one point this is one of the worst diseases you could possibly have. That meant so much to me.

I know very well that Dr Davis and Hanson are not on holiday. Dr Davis is a workhorse, who deprives himself of rest and luxury and any indulgence to get a the source of this nightmare. Dr Phair is also eager to help, as is Dr Hanson. The conference is a chance to state what was found, and to chat with old friends and new. These conferences are expensive, flights, hotels, catering. In today's world, with the internet, lots of this can be done on the internet. The research is not taking place here. It is often a good place to meet up with new contacts, or to have private talks with old ones. Dr Davis knows how desperate we all are. And you can sometimes hear a paper orally which will save you reading it later.

We need some serious answers, however. As Alvin I think said, we should have been here 30 years ago. And at this pace, well......

 

[Perrier]

So from the sounds of it T3 is not an issue but its having a stimulant effect but that effect is causing the disease to respond badly.
Thats useful information saying don't use it. Very unfortunate that many had to suffer to bring us this knowledge


I agree, we need a disease mechanism or at least an understanding of what the symptoms are being caused by. I also want to know what PEM is and why we get worse with exercise or over time. For many years i was more or less able to function but how long till PEM kept dropping to where i could not work. Then my ability till PEM dropped greatly as well as the interval. Plus the cognitive issues, wtf is causing them.
My impression is that we are where we should have been 30 years ago, if we get loads of funding today we could try to catch up in the next 5-10 years, but yous simply can't fully undo harms from the past.
I want to know the identity of the molecule causing the signal in Dr Davis nanoneedle, if w knew what it was it might help us identify the source and that may lead to a treatment or even cure. Then again it might be an incidental or even incorrect finding. We don't know till we try.

Alvin,
What you observe is correct. The T3 was having a stimulant effect. Many of the meds the CFS doctors gave had a stimulant effect. Then when a bit more movement was attempted and seemed to be sustained, oh Lordy Lord, the crash that came! There were even seizures on some occasions. And it was't like the exertions were 'normal.' Now, the crashes come but nothing much is attempted, and so they last 3 to 5 to 14 days instead of a whole year. So, it looks like boosting the system is not a good thing, at least this is our experience.

 

[Alvin]

Alvin,
What you observe is correct. The T3 was having a stimulant effect. Many of the meds the CFS doctors gave had a stimulant effect. Then when a bit more movement was attempted and seemed to be sustained, oh Lordy Lord, the crash that came! There were even seizures on some occasions. And it was't like the exertions were 'normal.' Now, the crashes come but nothing much is attempted, and so they last 3 to 5 to 14 days instead of a whole year. So, it looks like boosting the system is not a good thing, at least this is our experience.

Egads
So sorry to hear about this

 

[hixxy]

Has there been a write up anywhere with a summary of anything interesting from the symposium?

 

[Amw66]

Alvin,
What you observe is correct. The T3 was having a stimulant effect. Many of the meds the CFS doctors gave had a stimulant effect. Then when a bit more movement was attempted and seemed to be sustained, oh Lordy Lord, the crash that came! There were even seizures on some occasions. And it was't like the exertions were 'normal.' Now, the crashes come but nothing much is attempted, and so they last 3 to 5 to 14 days instead of a whole year. So, it looks like boosting the system is not a good thing, at least this is our experience.

Downregulation of T3 may be a protective measure. I think the hibernation hypothesis is an apt one. Something has gone very wrong and the body is in a protective mode until it can reboot?

The issue is where has it gone wrong?
If bistability is an issue there may be many more areas where this could be an effect

The interesting thing to me re IDO was the assumption that if one was missing, the other compensated was wrong. If this is the case, then it could be a similar story for many other genes, those with signalling function may be interesting.

 

[Alvin]

Downregulation of T3 may be a protective measure. I think the hibernation hypothesis is an apt one. Something has gone very wrong and the body is in a protective mode until it can reboot?

The issue is where has it gone wrong?
If bistability is an issue there may be many more areas where this could be an effect

The interesting thing to me re IDO was the assumption that if one was missing, the other compensated was wrong. If this is the case, then it could be a similar story for many other genes, those with signalling function may be interesting.

I don't disagree, i would guess that a immune mechanism is malfunctioning and we need to identify and manipulate it. Why its malfunctioning is also an important consideration, if we turn it off when it needed to be on then we may find there is an even bigger problem unleashed. But if its turned on because of a genetic flaw or malfunction then switching it off may cure us but if there is some bacteria/virus/invader at play then the immune system may not actually be malfunctioning and we need to target the causative agent and not the reacting immune system. So far little has been found to support this idea but we really need a mechanism to really know what we are playing with.

 

[Amw66]

I don't disagree, i would guess that a immune mechanism is malfunctioning and we need to identify and manipulate it. Why its malfunctioning is also an important consideration, if we turn it off when it needed to be on then we may find there is an even bigger problem unleashed. But if its turned on because of a genetic flaw or malfunction then switching it off may cure us but if there is some bacteria/virus/invader at play then the immune system may not actually be malfunctioning and we need to target the causative agent and not the reacting immune system. So far little has been found to support this idea but we really need a mechanism to really know what we are playing with.

Yes, I think the RNA research should be interesting. My daughter has symptoms of glandular fever during PEM, and we know that there is an immune issue as she had shingles in primary school, which is quite unusual. Herpes viruses seem ingenious, as no doubt are others.

Given Phair's focus on common SNPs etc, perhaps one worth considering is GTSM1 - this is involved with glucocorticoid sensitivity, oxidative stress, immune signalling, and it is not uncommon to have it deleted ( let alone have a SNP) - the thinking was that other GTSM genes would make up for it - but what if they don't.......

see de Vega's paper which highlights its role ( along with others) https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-017-0248-3

 

[FMMM1]

Downregulation of T3 may be a protective measure. I think the hibernation hypothesis is an apt one. Something has gone very wrong and the body is in a protective mode until it can reboot?

The issue is where has it gone wrong?
If bistability is an issue there may be many more areas where this could be an effect

The interesting thing to me re IDO was the assumption that if one was missing, the other compensated was wrong. If this is the case, then it could be a similar story for many other genes, those with signalling function may be interesting.

Regarding IDO1 and IDO2:

• IDO1 is substrate inhibited i.e. at higher tryptophan levels IDO1 stops working. I.e. stops converting tryptophan to kynurinine;
• IDO2 takes over at higher tryptophan levels.

So you need a substrate inhibited enzyme (like IDO1) and a second enzyme which operates at higher substrate levels (like IDO2). Phair has identified a further potential example; someone on this site reminded me of the compound - check my earlier posts if your interested.

I don't think there will be a lot of examples of two step systems where one is substrate inhibited - but I'm not a biochemist.

 

[lansbergen]

I don't disagree, i would guess that a immune mechanism is malfunctioning and we need to identify and manipulate it. Why its malfunctioning is also an important consideration, if we turn it off when it needed to be on then we may find there is an even bigger problem unleashed. But if its turned on because of a genetic flaw or malfunction then switching it off may cure us but if there is some bacteria/virus/invader at play then the immune system may not actually be malfunctioning and we need to target the causative agent and not the reacting immune system. So far little has been found to support this idea but we really need a mechanism to really know what we are playing with.

I think the immune system does what it needs to do but because the invader is very hard to destroy it produces toxic levels of the product that can destroy it.

If that toxic is what I think it is it would fit with the fact that levamisole helps me to improve.

Normal level of the product has many functions

 

[Alvin]

I think the immune system does what it needs to do but because the invader is very hard to destroy it produces toxic levels of the product that can destroy it.

If that toxic is what I think it is it would fit with the fact that levamisole helps me to improve.

Normal level of the product has many functions

Interesting. It could be.
Has anyone else tried that drug for ME?

 

[lansbergen]

Interesting. It could be.
Has anyone else tried that drug for ME?

I think 2 tried it for a short periode.

It has a bad reputation. I hasitated a long time because all the medical trained people I discussed it with warned me for the danger. When I was dying anyway the danger was the least of my worries.

 

[Perrier]

I think the immune system does what it needs to do but because the invader is very hard to destroy it produces toxic levels of the product that can destroy it.

If that toxic is what I think it is it would fit with the fact that levamisole helps me to improve.

Normal level of the product has many functions

Dear Landsbergen,
IN your post you say "If that toxic is what I think it is it would fit with the fact that levamisole helps me to improve."
Perhaps I missed some earlier posts of yours, but what toxic do you think it might be?

And Levamisole is a cancer drug, and yes, it is not used anymore in North America. And so I understand how the doctors said what they did. But what toxic are your referring to. Thanks.

 

[lansbergen]

Dear Landsbergen,
IN your post you say "If that toxic is what I think it is it would fit with the fact that levamisole helps me to improve."
Perhaps I missed some earlier posts of yours, but what toxic do you think it might be?

And Levamisole is a cancer drug, and yes, it is not used anymore in North America. And so I understand how the doctors said what they did. But what toxic are your referring to. Thanks.

Hydrogen peroxide in high concentration. That can destroy the pathogen I suspect.

 

[roller*]

@lansbergen

you mean, there is an invader and the immune system tries to fight that with producing endogenous hydrogen peroxide.

1) what invader could that be, that even resists high doses of hydrogen peroxide ?

2) why do you think its hydrogen peroxide ? the body could perhaps produce other things (too) ?

3) should be easy to figure if someone has too much hydrogen peroxide ?
e.g. just take some mms (miracle something supplement) - if it makes you vomit, you may have to0 much endogenous hydrogen peroxide already ?

4) why would levamisole help with too much hydrogen peroxide issues ?

(sorry, if i misunderstood what you were saying)