Community symposium on molecular basis of ME/CFS at Stanford Discussion Thread

[Ben H]

Does anyone know when the talks will be available on YouTube? I missed Ron's and Robert Phair's

Hi Ben.

When will these presentations be available on YouTube? Missed most of them yesterday.

Hi guys,

I'm not sure, it will take a little a little bit of time but as soon as I know you can be sure I'll let you guys know and update the thread (and probably start a new one too).

Hope everyone enjoyed it if you were able to watch or listen. It really was rather excellent!


B

 

[FMMM1]

Another cup of coffee calmed you down?

You are much more of a scientist than I am, and I don't want to derail this thread but wanted to point you to these studies which indicate that BCAAs can play a role in reducing tryptophan and that high tryptophan can cause something called central fatigue. And many members (including myself) have had some benefit from taking BCAAs. So in case you were inclined to start a tryptophan thread, I thought these might be useful (or not!)

http://www.ncf-net.org/forum/Fword.htm
http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=41341
http://jn.nutrition.org/content/136/2/544S.full
http://www.ncbi.nlm.nih.gov/pubmed/11310928
http://www.sportsci.org/jour/9901/rbk.html

Hi Mary.

I only watched a few minutes of Ron's talk. From memory Ron emphasised the need to develop a diagnostic test -- the fact -- that this was not a race -- that others were making good progress -- i.e. it doesn't matter who delivers the test.

I agree that the delivery of a diagnostic test, available to everyone, is important. I also think that it's achievable with existing technology e.g. here's a potential blood based diagnostic test:
1) abstract: https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01437j/unauth#!divAbstract;
2) full paper: https://sci-hub.se/10.1039/C8AN01437J.
Ron discusses other currently viable options e.g. Seahorse.

I've asked the European Union (EU) Committee on the Environment, Public Health and Food Safety (ENVI) if they would lobby for funding for a study to see if this can be used as a diagnostic test. Currently this Committee are lobbying for increased funding for research into Lyme disease, including the development of a diagnostic test for Lyme disease. The EU has already funded the development of an improved diagnostic test for Lyme [2 million euros/dollars]. The EU has not funded any research into ME/CFS.

I'd be grateful if readers would contact their elected representative, e.g. Member of the European Parliament, to ask that public funding is made available for the development of a diagnostic test for ME/CFS. You may find something useful in this thread/blog [https://forums.phoenixrising.me/ind...h-theyre-working-for-you.61516/#post-1001161].

 

[Ben H]

B

 

[lindaso1]

I think 'quiet hope' might be appropriate right now

But you're right, he sure didn't skimp on details


B

At the end, Davis & Phair essentially said that although they havent done all the testing needed, people are suffering and in good conscience they werent going to hold the info in till them and they were putting the info out. Tears... They cautioned against self experimentation. They also encouraged all of the researchers to share their findings and collaborate before their studies were published. It was a really brave, selfless moment on their part.

I took notes:
Phair said that they have been working on it for 8 months. All their research shows if this happens, there is no way to overcome it without intervention. The issue is due to "mutation bi-stability." The "IDO2 protein does not work." "IDO1 is substrate inhibited." Thus "the cellular tryptophan (in IDO2) is increased, kynurenine decreased"which "limits serotonin and NAD production, which controls the immune system." He said "inhibition of IDO1 causes fatigue" and we want to "activate the IDO1 gene." He said we already have a cancer drug that does that. He did say that serotonin levels could either be high or low.

Hope this helps...

 

[Diwi9]

Can anyone post the handouts that were available this morning? I didn't get a chance to download them, and now I can't see them anymore. I DID find the agenda and Dr. Davis's letter, but I assume there's more, like there was last year.

RWP

I'm traveling today, so can't post, but the rest of the handouts were just short bios of each speaker and a symposium evaluation form.

 

[Sing]

A couple more notes about Rob Phair’s talk—all in my words, unless I quote:

He finds it significant that sometimes ME/CFS occurs in an epidemic fashion. That means that whatever predisposing genetic mutations there are must be common. To me this conclusion from the evidence of epidemic instances means that research trying to find the genetic mutations invovled and that could be causal is a waste of time!

What these common genetic mutations dois to “produce or uncover bistability”, the tendency to move from a steady state of healthiness to a steady state of unhealthiness. ME/CFS is “not sustained by something acutely broken but by a design defect in our biological system” —to go from a healthy steady state to an unhealthy steady state and get stuck there..

Without kynurenine he said that you can’t suppress autoimmunity, and both ATP and NAD will be limited. We know what ATP does. NAD also does many things.

If you take or have too much Tryptophan, it can cause autoimmunity.

When serotonin levels are too high, our receptors become less sensitive and the body no longer knows what is normal. The serotonin level could be high or low depending on—did he say, cell type?

Depressed kynurenine has many powerful effects itself.

I apologize that I could not catch all of this precisely (overtired brain), but maybe someone else can add to or correct my notes on this part of Phair’s talk. His talk and others deserve very close attention once we get the videos, so we understand with accuracy the points that were made.

 

[Ben H]

A couple more notes about Rob Phair’s talk—all in my words, unless I quote:

He finds it significant that sometimes ME/CFS occurs in an epidemic fashion. That means that whatever predisposing genetic mutations there are must be common. To me this conclusion from the evidence of epidemic instances means that research trying to find the genetic mutations invovled and that could be causal is a waste of time!

What these common genetic mutations dois to “produce or uncover bistability”, the tendency to move from a steady state of healthiness to a steady state of unhealthiness. ME/CFS is “not sustained by something acutely broken but by a design defect in our biological system” —to go from a healthy steady state to an unhealthy steady state and get stuck there..

Without kyuernine (spelling?) he said that you can’t suppress autoimmunity, and both ATP and NAD will be limited. We know what ATP does. NAD also does many things.

If you take or have too much Tryptophan, it can cause autoimmunity.

When serotonin levels are too high, our receptors become less sensitive and the body no longer knows what is normal. The serotonin level could be high or low depending on—did he say, cell type?

Depressed kyuernine has many powerful effects itself.

I apologize for how I could not catch all of this (due to an overtired brain) but hope that my adding these notes on Phair’s talk, it may nudge someone else to fill in the blanks. In any case, his talk—along with the others—deserves close attention once we get the recordings.

Hi @Sing

My bold. May I ask why?

The outbreaks have always been a point of contention and this is potentially one way to explain it. Prof. Phair is very plain to point out this is simply a hypothesis-albeit one that holds up so far-and may very well be wrong.

I personally find it logical though admit it seems an against-the-grain take on mutations in a field where it is usual to focus on the rarer mutations, where the common ones are given much less interest.

His hypothesis helps explain the huge amount of people suffering from mecfs, or at least part of the spectrum that may be mecfs. The fact that he acknowledged the outbreaks to demonstrate this does not at all exclude the individuals that develop it/the majority. Though I'm not suggesting you are saying this.

It is simply a hypothesis at the end of the day. There are no absolutes.

I'm really, really tired so please excuse any lack of coherence.


B

 

[ljimbo423]

I was very impressed with Jarod Youngers talk about a weakened blood brain barrier (BBB) and neuro-inflammation and how that could cause the fatigue, flu-like symptoms, PEM, etc. seen in ME/CFS.

This abstract might explain a possible cause of that weakened BBB.

Research has been very consistent about significant dysbiosis in ME/CFS. I also have links to 6 ME/CFS studies that show higher levels of lipopolysaccharides (from bacteria in the gut) in the blood of ME/CFS patients verses controls.

Showing increased intestinal permeability (leaky gut) in ME/CFS-

Abstract
A growing body of evidence indicates that the microbiome interacts with the central nervous system (CNS) and can regulate many of its functions. One mechanism for this interaction is at the level of the blood-brain barriers (BBBs).

In this minireview, we examine the several ways the microbiome is known to interact with the CNS barriers. Bacteria can directly release factors into the systemic circulation or can translocate into blood. Once in the blood, the microbiome and its factors can alter peripheral immune cells to promote interactions with the BBB and ultimately with other elements of the neurovascular unit.

Younger also talked about trying to make a connection between the neuro-inflammation in ME/CFS and peripheral immune activation....

Bacteria and their factors or cytokines and other immune-active substances released from peripheral sites under the influence of the microbiome can cross the BBB, alter BBB integrity, change BBB transport rates, or induce release of neuroimmune substances from the barrier cells.

I think he also mentioned thinking that B cells and T cells were getting through the BBB and possibly causing microglial activation and inflammation-

The intestine also contains a barrier, and bacterial factors can translocate to the blood and interact with host immune cells.

These metastatic bacterial factors can signal T-cells to become more CNS penetrant, thus providing a novel intervention for treating CNS disease.

Future research should begin to define the bacterial species that can cause immune cells to differentiate and how these interactions vary amongst CNS disease models.

Link to Abstract

 

[Sing]

I want to add that it was amazing that I made it to the Saturday talks and even partly cogniscent of all that was going on. Totally worth it though rather dead on my feet. I would highly recommend going to this event next year for any of us who can possibly make it. It felt as though I was walking among legends, that history is in the making. I never felt this so vividly and directly. The room was full of great people—working group, patients and caregivers. The feeling of intimate and intelligent involvement and community spirit are evident and strong. Big Love! We patients are the reason as well as their partners in this work. There is a great team here and I know we can expect wonderful results.

 

[Moof]

Oh, I'm so excited now to see Ron's and Robert's presentations, having read what people have said! They were in the middle of the night in the UK – the event started at 5pm our time, and I only managed to stay with it until the lunch break before I fell asleep. It all sounds incredibly positive.

 

[Gemini]

I think he [Younger} also mentioned thinking that B cells and T cells were getting through the BBB and possibly causing microglial activation and inflammation-

I made a note @ljimbo423 that he said he's received a UK grant to pursue this. Be interesting to know what methods he'll use to detect T and B cells and when he expects to have answers.[/QUOTE]

 

[ljimbo423]

I made a note @ljimbo423 that he said he's received a UK grant to pursue this. Be interesting to know what methods he'll use to detect T and B cells and when he expects to have answers.

Younger gave a 1 year reference to something but I don't remember if it was for the B and T cell passage through the blood brain barrier or something else. Do you remember?

 

[wigglethemouse]

I made a note @ljimbo423 that he said he's received a UK grant to pursue this. Be interesting to know what methods he'll use to detect T and B cells and when he expects to have answers.

Cort wrote about it a few days ago
https://www.healthrising.org/blog/2018/09/25/invasion-neuroinflammation-chronic-fatigue-syndrome/

 

[wigglethemouse]

To me this conclusion from the evidence of epidemic instances means that research trying to find the genetic mutations invovled and that could be causal is a waste of time!

At the 2017 Symposium Neil McGregor proposed genetics play a role in which symptoms patients have

Transcript:
https://www.melbournebioanalytics.o...mecfs-by-neil-mcgregor-written-transcription/

 

[ljimbo423]

I made a note @ljimbo423 that he said he's received a UK grant to pursue this. Be interesting to know what methods he'll use to detect T and B cells

This is a quote from the link above provided by @wigglethemouse

Younger’s going to pull ME/CFS patients’ blood, isolate their T and B-cells and then incubate them with a new Zirconium 89 tracer which slides through the cell membranes but does not damage them.

He fully expects ME/CFS patients’ brains to light up like candles. Similarly, he doesn’t expect to see any light shows coming from the healthy controls.

link

 

[Gemini]

Younger gave a 1 year reference to something but I don't remember if it was for the B and T cell passage through the blood brain barrier or something else. Do you remember?

@ljimbo423 yes, I think he said it about that study; will have to re-listen to be sure though (it was a long day).

Reviewing his brain temperature study he mentioned "cooling" it down. Did he describe how to do it does anyone remember?

 

[ljimbo423]

yes, I think he said it about that study; will have to re-listen to be sure though (it was a long day).

Yes, it was along day for me too, I watched the whole symposium.

Reviewing his brain temperature study he mentioned "cooling" it down. Did he describe how to do it does anyone remember?

I don't remember him saying how to cool down the brain but I might have missed it. I wonder if that's why some people get a reduction in symptoms from "cold therapy"? IE, cold showers etc.

 

[Tally]

A long time ago Cort Johnson mentioned Younger talking about brain temperature in one of his articles. If I remember correctly there was also a researcher that built a cooling device for forehead to help people with insomnia.

Since then I use a very crude device called a wet rag that I put on my forehead when I can't sleep or when I'm crashed. It helps a bit but it only cools my forehead and it goes from too hot to too cold quickly and then I have to remove it.

I wish there was a way to cool the whole head and cool it just a tiny bit.

 

[pamojja]

I wish there was a way to cool the whole head and cool it just a tiny bit.

This side https://www.selfhacked.com/blog/12-reasons-embrace-cold/, talks about a Cryohelmet: http://www.cryohelmet.com/

 

[shoponl]

I wish there was a way to cool the whole head and cool it just a tiny bit.

Would a flexible gel ice pack in a dry washcloth or fleece wrap work? They stay cool for a half-hour or so.
https://www.amazon.com/Reusable-Cold-Pack-Compress-rehabilitation/dp/B01N3XQFS0

Or an ice hat? there are also bandannas, face compresses, etc. from different companies.
https://www.amazon.com/Headache-Hat-Original-Wearable-Headaches/dp/B00FGWLDR6

I tried the gel eye mask years ago, but it warmed quickly.