NIH's "Accelerating Research on ME/CFS" Conference April 4-5, 2019 - livestreaming

RYO

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Watching conference too long triggered PEM.

There was some rehash of information along with some new findings.

The broadest perspective suggests ME/CFS is a heterogeneous disease involving neurologic and autonomic nervous system perturbation. It is unclear to me whether mitochondrial dysfunction is an independent abnormality triggered by immune system dysregulation vs the result of microcirculation dysfunction.

NIH intramural study will eventually provide trove of data for many years. Preliminary results interesting. What is causing low B Cells in CSF?

I suspect that the greatest strength of NIH intramural approach will turn out to be their fairly narrow inclusion criteria.

In my opinion, the most fruitful areas of research that need further investigation are:

- metabolic, neurologic, and immunologic response to exercise challenge in ME/CFS patients (I suspect the muscle biopsies collected will be prove to be valuable). What is it about exercise that triggers PEM? Is it just exacerbation of low volume state? Does exercise trigger neuroinflammation? Does exercise trigger abnormal immune response?

- go beyond looking at data from "omics" to finding tissue level pathphysiology (Ron Davis's team may be particularly helpful in developing new technologies to measure in vivo organism level biologic processes)

- validate MRI spectroscopy data. What does MRI spectroscopy look like in other disease states (Alzheimer's, Parkinson's, Depression, Mitochondrial disease, Multiple sclerosis)

Lastly, the NIH intramural study of ME/CFS points out the inherent difficulty of evaluating patients who suffer with debilitating fatigue. Much work still needs to be done to help clinicians work through the methodical steps of determining the etiology of often non specific symptoms. The ultimate diagnosis may be ME/CFS but there are other disease states such as undiagnosed cancer and myositis that are often not apparent in initial workup. Perhaps this an avenue to pursue in at least introducing ME/CFS as a topic to teach in medical schools and residency programs.
 
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Wally

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FYI - there is another thread that has been opened about exosomes at https://forums.phoenixrising.me/threads/research-re-exosomes-and-me-csf.75840/. Forum moderators are currently reviewing whether or not the exosomes related posts on this NIH Conference thread will be combined with this more specific thread related to exosomes. If the two threads are combined the Forum moderator will post this information.
 
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Gemini

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An estimate, give or take, of start times for videocast speakers. Each presentation lasts about 30 minutes:

Day 1

Bateman 19:00
Naviaux 55:00
Fiehn 1:30:00
Berquist 2:04:00
Montoya 2:35:00
M. Davis 3:07:00
Unutmaz 3:35:00
Hanson 4:00:00
Klimas 4:26:00
Systrom 4:55:00
Keller 5:23:00
Moreau 5:59:00

Day 2

Francis Collins 1:23:00
Walitt 1:34:00
Lipkin 2:08:00
Oh 2.32.00
Prusty 3:05:00
R. Davis 3.32:00
Younger 4:05:00
VanElzakker 4:32:00
Rowe 5:05:00
Oaklander 5:32:00
Komaroff 6:02:00
 
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Just watched the Prusty talk. It is very good. You can find at the 3:05 mark in this video

https://videocast.nih.gov/summary.asp?Live=31640&bhcp=1

he has some excellent microscopy on mitochondria and shows how they react to being put in MECFS serum, and how they recover when they come back out of the serum. All his stuff is on mitochondrial fragmentation. They're not supposed ot be little beans like they look in the textbook. He says they should be long strands that merge with one another. But when they get hit by a virus they get fragmented. That fragmentation also happens when you put cells in MECFS serum, he says.

Screen Shot 2019-04-13 at 6.13.27 pm.png
 

raghav

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I am surprised that no other researcher has noticed the fact of mitochondrial fission and fusion. It was written in text books and medical journals that mitochondria are rigid structures and each mitochondria is a bean like structure and penetrating it is a tough task for drug designers.

But according to Prusty there are many factors which can be manipulated in our favour to increase the fusion of mitochondria and hence increase mitochondrial respiration and production of ATP. I am a layman as far as mitochondria are concerned. But when my neurologist diagnosed my left hippocampal sclerosis 12 years ago he said I have a mitochondrial mutation and nothing can be done about it. So I was initially very dejected. But now there seems to be some hope.

Prusty's presentation is a must watch for everybody.
 
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The idea that exercise causes something to be released into the blood, (exosomes with a load of a hitherto hidden viral substance?) and that causes mitochondrial fission that makes us sick and weak for several days, makes sense to me.

I'd be interested to look at the nanoneedle and see what the mitochondria are doing while the impedance goes up. Could mitochondrial fission change impedance?

if this route works out, there does seem to be an inhibitor of fission called mdivi. It's for sale as a research chemical: https://www.sigmaaldrich.com/catalog/product/sigma/m0199?lang=en&region=US
 

Wally

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@Murph, @raghav - Interesting info. re mdivi (*).

I found this paper published in 2016 about “quinazolinine”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794932/
It sure seems like we keep circling around some of the same puzzle pieces.
Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities

Quinazolinones and quinazolines are noteworthy in medicinal chemistry, because of wide range of their antibacterial, antifungal (1,2,3,4,5,6), antiinflammatory (7,8), antimalaria (9), anti-HIV (10), antiviral (10,11), antituberculosis (1,12) properties and also their inhibitory effects on thymidylate synthase (13,14), poly-(ADP-ribose) polymerase (PARP) (15,16,17) and thyrosine kinase (18,19). There are several approved drugs with quinazoline structure in the market such as, prazosin hydrochloride, doxazosine mesylate and terazosine hydrochloride (20,21)....
(*) https://www.ncbi.nlm.nih.gov/pubmed/28842943 - “To mdivi-1 or not to mdivi-1: Is that the question”
[Edit to add links to these papers - 1) https://www.ncbi.nlm.nih.gov/pubmed/28790012 - “Mdivi-1 ameliorates early brain injury after subarachnoid hemorrhage via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.”
2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003121/ - “Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients”
 
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junkcrap50

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Interesting info. re mdivi (*).
(*) https://www.ncbi.nlm.nih.gov/pubmed/28842943 - “To mdivi-1 or not to mdivi-1: Is that the question”
[Edit to add links to these papers - 1) https://www.ncbi.nlm.nih.gov/pubmed/28790012 - “Mdivi-1 ameliorates early brain injury after subarachnoid hemorrhage via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.”
An interesting quote from the abstract: "In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress..."
Is there any mito complex problems in CFS or which complex/step? Or does it all appear to work normally?
 

Wally

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I have started another thread which has links to Miriam Tucker’s two articles published in Medscape re the NIH Conference. https://forums.phoenixrising.me/threads/“‘milestone-meeting-highlights-nih-efforts-to-combat-me-cfs”-4-17-2019-article-by-miriam-tucker-published-in-medscape.75941/#post-2198040

For those you are not aware of what “Medscape” is and why it is significant when articles are published in this venue here is a short description about Medscape from Wikipedia.

Medscape is a website providing access to medical information for clinicians; the organization also provides continuing education for physicians and health professionals. It references medical journal articles, CME (Continuing Medical Education), a version of the National Library of Medicine's MEDLINE database, medical news, and drug information (Medscape Drug Reference, or MDR). At one time Medscape published seven electronic peer reviewed journals.[2]

Date launched: May 1995
Owner: WebMD
 

Wally

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Oh, when will these lovely hard working folks announce that they know what is wrong with ME patients, what the real nature of this disease is, and when will there be treatments. These conferences are really fascinating, lots of experiments, and this is found and that is found, but when oh when will we have a complete picture and a real sense of what this disease is, and how to fix it. It is very hard waiting and watching our children and friends suffer so deeply
They haven't figured yet.