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

[Gemini]

I hope someone will create a time index [of the livestream video] so we can zoom in and review specific presentations.

@shoponl, rough estimates, give or take, of start times for the speaker's talks:

Raeka Aiyar--24:00
Oystein Fluge--35:00
Wenzhong Xiao--1:11:00
Jonas Bergquist--1:33:10
Alain Moreau--2:26:35
Maureen Hanson--2:49:12
Ron Tompkins--4:55:32
Michael Sikora--5:06:03
Jarred Younger--5:27:53
Ron Davis--6:24:49
Robert Phair--6:38:04
Ron Davis--7:11:00

Panel discussions are after Maureen Hanson and at the end after Ron Davis.

@Janet Dafoe (Rose49) @AshleyHalcyoneH

 

[WinterWren]

Tryptophan and pregnancy - just been reading about it and how it's need is greater during pregnancy... got me thinking about how so many of us feel better when we are pregnant... are we using up all the tryptophan that is at excessive levels as phair describes that ordinarily is making us feel like crap?....

I was thinking about pregnancy too. I think it's this study that says it's common to have a more difficult first trimester (then healthy pregnancies) and then about 30% go on to experience improvement in ME symptoms https://www.ncbi.nlm.nih.gov/pubmed/14980991

Which goes along with feeling worse before you feel better (that was my experience, horrible and then almost full remission).

 

[Jackb23]

Can I ask what your 3 worst symptoms are? Just wondering if they might be more related to the neuro-inflammation Jarod Younger talked about at the symposium.

3 worst symptoms are cognitive dysfunction (visual symptoms, memory problems, balance issues) these worsen after exercise, altered sleep schedule/hypersomnia, and serotonin syndrome from anything that remotely increases serotonin such as dextromethorphan. I can definitely see how the metabolic trap hypothesis would feed sickness behavior in the brain. The kynurenine pathway has been heavily implicated in many neurodegenerative diseases as well as some neuropsychiatric conditions.

 

[shoponl]

rough estimates, give or take, of start times for the speaker's talks

Very useful, thank you!

 

[Vassie]

Didn't Dr Chia try using this?

Yes, he used interferon in the past.
But gamma only in combination with alpha, I think.

https://me-pedia.org/wiki/Interferon#Dr_Chia.27s_investigation_of_interferon.C2.A0therapy.C2.A0

https://phoenixrising.me/treating-c...ing-chronic-fatigue-syndrome-mecfs-interferon

 

[sb4]

Is the SNP rs10109853

Yeah. I think CC is the wild type so TT would be variant. As you can see from this graph at the bottom of the page. CC is only like 25% of Europeans so the mutation is very common.

 

[mariovitali]

Here are some comments , along with results given through Machine Learning :

cc : @Janet Dafoe (Rose49)

ALAIN MOREAU :

approx @ 2:46:21 He talks about TSP-1 (aka THBS1) being upregulated.

Here is slide 47 from my presentation at EUROMENE, you can see where TSP-1 is located :

Unfortunately i do not have the knowledge to comment but perhaps TSP-1 is upregulated for a reason (he talks about inhibiting it so that ME/CFS Symptoms are ameliorated).


MICHAEL SAKORA

@5:22:53 He shows a heatmap of Genes with clonally expanded cells (i am not sure if i got this right). In the figure below i annotated two Genes, namely FASLG (FAS Ligand) and MYO6 :

Post at Twitter , August 2017 :

The system got FASLG and a near hit (?) for MYO6 -got instead MYO9B- but both MYO6 and MYO9B are relevant to actin binding and actin filaments.

See also the relevant post here (August 2017) :


http://algogenomics.blogspot.com/2017/08/new-findings-myosin-d3-actins.html


JARRED YOUNGER

@5:40:12 He talks about elevated Lactate. Machine Learning confirms the relevance of this finding to ME/CFS :


Slide 25, Machine Learning ranks lactate on the top 5 positions :

JONAS BERQUIST

@1:50:17 he talks about downregulated Pregnenolone. For this a gene called TSPO may have a part :

From my presentation :

So how does this fit in Jonas Berquist findings ? Please see where TSPO is located below :

 

[Moof]

Yeah. I think CC is the wild type so TT would be variant. As you can see from this graph at the bottom of the page. CC is only like 25% of Europeans so the mutation is very common.

Thank you. Do you know the rs number and variant allele for the Y359stop mutation, by any chance? I understand that individual SNPs often aren't meaningful in isolation, and that commercial genetic testing isn't nearly as accurate as that done by specialist labs, etc etc...it's just that the focus on it has made me curious!

 

[sb4]

Do you know the rs number and variant allele for the Y359stop mutation, by any chance?

Just looked it up now it's this one. TT is the wild type (more than 50% of Europeans are wild type). I am A/T. I am unsure on how much this inactivates IDO2 but from skimming a few studies it does appear to reduce it somewhat. If anyone knows please let me know.

 

[Moof]

@sb4, thanks for that. I tried to find the rs number by searching for Y359stop, but couldn't! The stop/stop variant completely inactivates IDO2 (and thus may protect from cancer); I'm less sure about stop/WT, but it may reduce the activity and provide some protection.

 

[FMMM1]

Is the SNP rs10109853? (Sorry, your link goes through to 23andMe, the site asks you to sign in before seeing the info, and I can't find my password!)

If so, I have homozygous TT. I don't know whether that's the version that could potentially reduce ID02 activity, though.

If you check out Phair's talk then I think he says that modelling [there's a specific reference on the slide to the software he used] indicates that any of the mutations (4 or 5?) will mean that IDO2 will not work. The only difference is frequency one is remarkably common i.e. greater than 40% of the population. There's one that doesn't even make the protein.

 

[FMMM1]

But how do they know whether this graph is specific to CFS? I mean, in the graph it says they have checked this against healthy controls, but have they also checked it against people with other diseases, to see if they don't show the same pattern? Otherwise you might get a lot of false positives (although I guess this is less of an issue than false negatives).

There are other potential test e.g. this measures intracellular phenylalanine in blood cells using Raman spectroscopy:
1) abstract: https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01437j/unauth#!divAbstract;
2) full paper: https://sci-hub.se/10.1039/C8AN01437J.

At the moment this might be easier to explain i.e. it measures phenylalanine which Chris Armstrong, and Fluge and Mella, found to be reduced in blood plasma in ME/CFS [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229 & https://minerva-access.unimelb.edu....g Metabolomics CFS.pdf?sequence=5&isAllowed=y]. Armstrong, and Fluge and Mella, proposed that phenylalanine (and trypophan etc.) were being used cellular energy production/ATP- switch from using glucose.

At this stage I'd like to see a diagnostic method which measures the proposed causal agent i.e. high intracellular trypophan. Don't know if you could measure intracellular trypophan using Raman spectroscopy.

Here's a bit about lobby for funding for a diagnostic test https://forums.phoenixrising.me/ind...ch-theyre-working-for-you.61516/#post-1003111.

 

[sb4]

I tried to find the rs number by searching for Y359stop, but couldn't!

Yeah I struggle with this all the time, there has to be a better way to find the rs for SNPs. I just googled Y359stop and started going through all the results, with ctrl + f until I found one that had the rs number with it.

As I skimmed through I read some studies that suggested that the hetero version does cause some inhibition.

 

[JES]

@sb4 Nice finding, sometimes you don't realize how Ctrl+F can make your life easier.

According to 23andme, I have the T/T homozygous variant of rs4503083/Y359stop. Now I just need to figure out which variant, A or T, is the problematic one...

 

[Moof]

@sb4 Nice finding, sometimes you don't realize how Ctrl+F can make your life easier.

According to 23andme, I have the T/T homozygous variant of rs4503083/Y359stop. Now I just need to figure out which variant, A or T, is the problematic one...

I believe T is the wild/normal type, so there is no premature stop. However, according to Dr Phair's presentation, this was just one of five mutations that can have an effect on IDO2:

I don't have the Y359stop either, but am homozygous for the very common damaging allele on R248W – which could reduce the activity of IDO2 by 90% or more. This was present in 55% of the severely ill patients, and 42% of the 1000 Genomes sample which represents populations of European ancestry.

It'll be very interesting to see if Dr Phair's theory about IDO2 is proven or not.

EDIT: The description 'damaging' may be debatable, since research suggests that people with reduced IDO2 function may well be protected from some cancers!

 

[Neunistiva]

I watched the live stream of this year's Symposium with a faint hope of hearing about a cure even though I knew it is waaay too soon. I was afraid of being disappointed because research is slow work but instead I feel really good about what I have seen and heard.

I was happy to see these excellent scientist putting their efforts into our cause. I was touched that Dr. Phair donated his time.

I see their hard work, their enthusiasm and dedication. I know for sure they are not in it for the fame. These experts show amazing degree of modesty, willingness to share their expertise and openness to collaboration. Really refreshing to see.

These people deserve so much more from all of us.

I feel heartbroken for my daughter suffering with severe ME until I think of Whitney, I feel sad for my hardworking husband until I see dr. Davis, I feel bad for myself until I read what dr. Janet Dafoe has written.

And I must say I AM IMPRESSED. I’m impressed with their whole family. They warm my heart, they make me feel better, they give me hope.

I felt tired just watching the Symposium and then I read today that Dr. Davis went on a 3 day retreat with Stanford Biochem Deptment to talk about metabolic trap. I immensely admire what he is doing for ME/CFS community. He's really a hero. I only wish there were more people like him in this world.

I thank all the scientist and their supporter trying to get to the bottom of this awfull illness.

@Janet Dafoe (Rose49) @AshleyHalcyoneH @ChrisArmstrong

 

[Navid]

[
I felt tired just watching the Symposium and then I read today that Dr. Davis went on a 3 day retreat with Stanford Biochem Deptment to talk about metabolic trap. I immensely admire what he is doing for ME/CFS community. He's really a hero. I only wish there were more people like him in this world.

Hi:

Where did you read that the Biochem Dept went on a 3 day retreat? Just curious.
Thanks

 

[Neunistiva]

Where did you read that the Biochem Dept went on a 3 day retreat?

https://twitter.com/i/web/status/1047256693761966080

 

[Navid]

https://twitter.com/i/web/status/1047256693761966080

Thank you!!!!

 

[theflo]

So, the Davis/Phair talk is amazing.

I myself have been in a very bad crash this summer, and recently started supplementing with 5-htp: I saw radical improvement after my first dose, and within 10 days I was able to walk for 5 minutes, something I hadn't been able to do in 4 months.

So I'm a little heartbroken to hear about this possible metabolic trap, and the implications of possible high serotonin / reduced serotonin receptors in the brain, and the possible effect of tryp/5htp supplementation.

Here are my questions. Ron says not to self-medicate and not to experiment. I understand why he says that. I understand that these pathways are super critical.

I'm being followed by an MD (however uneducated about ME) and an ND, so I'm not completely "self medicating".

Just want to hear about patients' reactions to this - are you considering stopping SSRIs, 5-htp, etc? What about mineral supplementation? My knowledge of biology is minimal and I'm trying to weigh the risks of trying some supplements to get me out of this big crash.

How are you all navigating your meds with this new information?
Your thoughts are welcome