Research Re Exosomes and ME/CSF

[Rufous McKinney]

We had lightening last nite. I didn't hear any thunder, and don't know where this came from, as its been very foggy here.

so I was told today a joke: Did I see the thunder, and hear the lightening?

I laugh. Missed entirely the joke. Details. Cognitive details.

 

[Marylib]

The swiss cheese analogy: yup. Today I plan to: attempt to put new thread on this sewing machine bobbin. The tension is off, something is wrong, I just: rather stare it blankly. I cognitively just don't seem to be able to complete the various cognitive steps to: resolve that minor issue. Its very strange to just sorrta- watch oneself, as a neutral observer. And the visual dilemmas as well. Cannot thread the needle: tried all methods.

Its remarkable to witness. Yet brain is in fact still in there. I'm sure of it.

Yes it is still in there last time I checked...

 

[Wally]

Some additional discussion and links re exosomes can be found at this thread (see Reply # 74, #75 and #76) https://forums.phoenixrising.me/threads/brain-on-fire-widespread-neuroinflammation-found-in-me-cfs-by-jarred-younger.61580/page-4

Whatever, your theory (bottom up/top down - Phair) you have to be able to explain the plasma switching reversal in cellular energy/mitochondria morphology (Prusty - the mitochondria change shape/it's reversible) and yes central nervous system problems (brain). Exosomes, seem to me to provide the "signalling" to explain this cascade - fatigue --. Fluge and Mella suggested a signalling problem in 2006: "ME/CFS is caused by immune interference with an unidentified target, potentially a signaling factor, which ultimately causes metabolic dysfunction and in" [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/].

 

[FMMM1]

========================
Perrier:
Thanks for your optimism, and information.
I looked at the link to Hanson's work. And if these vesicles are exploding in the blood, how would one control them. And why would they explode. And are there other illnesses which have this component. I may not be getting the mechanism right here, and would appreciate any input to this subject which you have brought up. Very interesting.

This something in the serum evidence to me looks massive. If indeed our m.e cells revert to normal (wow!!!!!!!!!) in healthy serum, then surely this is the closest to a cure for us? I mean, our poor cells can actually be normalised! That's something huge! Army idea why this isn't bring pursued massively? (It doesn't appear like it is as I first heard about this in 2016, and there's been no advance except the offender is now mentioned as an exosome)[/QUOTE]

I agree that this looks massive i.e. the discovery of mitochondrial fragmentation in ME and the fact that it disappears when the exosomes are filtered out of the plasma. Also, the association that microRNAs from HHV-6A virus cause mitochondrial fragmentation, i.e. to avoid the immune response, and that this it is likely that other virus's and bacteria can fragment mitochondria.

Francis Collins (Director NIH), in his speech at last months ME Conference, (from memory) highlighted that breakthroughs often come from new (young) researchers who've been working in unrelated areas. Also, Cort Johnson highlighted (before Bhupresh Prusty spoke) that NIH were expecting big things - that's why he was invited by NIH. So NIH appear to recognise the potential importance of these findings.

I'm also surprised that so little has been made of Bhupresh's findings. E.g. why no announcement of funding for a mitochondrial fragmentation study in ME, and Lyme, and a study of microRNAs (in exosomes) which cause mitochondrial fragmentation? However, that possibly reflects my lack of knowledge of how long it takes to allocate NIH funding - even to the NIH funded ME/CFS Research Centres.

I think it will require a large scale study to establish how common mitochondrial fragmentation is in ME and the role of microRNAs in exosomes. Jan Brea's announcement, that the basis of her ME was neurological, highlights that we each need a definitive diagnosis as soon as possible - those reading this may have mitochondrial fragmentation caused by microRNAs (in exosomes) or not.

ME Action are lobbying for the development of a diagnostic test and treatments for ME https://www.meaction.net/…/announcing-millionsmissing-2019…/

 

[keepontruckin]

Until conversations take place at the top of Health Canada and the NIH that the numbers of people with me/cfs warrant funding I guess the status quo or something close to it is their target. The view is that there are not enough lives affected.

 

[FMMM1]

Until conversations take place at the top of Health Canada and the NIH that the numbers of people with me/cfs warrant funding I guess the status quo or something close to it is their target. The view is that there are not enough lives affected.

Hi if you look at Europe (EU); Lyme disease affects approximately 1 million people and the EU provided 33.9 million euros (roughly US dollars) for biomedical research in 10 years.

ME affects approximately 2 million people in the EU; so ME got roughly 70 million euros - correct? No, ME got zero - that's right nothing.

If you check out ME Action's website you'll find this discrepancy in funding for diseases is not unusual. Liver damage from alcohol is not funded because it is considered to be self inflicted - ME is not funded because it is seen as psychological (and thereby self inflicted). Even Lyme is labelled to some extent as psychological; so those with Lyme considered it underfunded.
This inequity in funding [based on severity/numbers affected] also turns up in the OMF presentations - think Hanson --- Google something like "ME funding inequality Hanson" or "health funding inequality ME" you'll find a bunch of stuff.

A biomedical test for ME would change that - in EU terms, even if we got funding proportionate to Lyme (twice Lyme to account for numbers) then that would be a significant improvement.

ME Action are lobbying for the development of a diagnostic test and treatments for ME https://www.meaction.net/…/announcing-millionsmissing-2019…/

 

[wigglethemouse]

This paper on Exosomes has an interesting snippet. In fact the whole paper is worth a read if you are interested in learning more about exosomes.

Exosomes also contribute to creating an immunosuppressive microenvironment by inducing apoptosis and impairing the function of effector T cells and natural killer cells (NKs), inhibiting dendritic cell (DC) differentiation, expanding myeloid-derived suppressor cells (MDSCs), and promoting regulatory T cell (Treg) activity.

This article talks about differences seen in testing of NK cells by different research groups and perhaps it could be due to whether or not the NK cells are tested in the presence of blood or not.
https://www.healthrising.org/blog/2...-fatigue-syndrome-and-u-k-me-cfs-researchers/

 

[kms1990]

If they do determine exosomes are causing aspects of CFS, what are the proposed treatments? Or are we at too early a stage to even go there?

 

[FMMM1]

If they do determine exosomes are causing aspects of CFS, what are the proposed treatments? Or are we at too early a stage to even go there?

Check out Ron Davis talk at last month's NIH Conference. Ron mentions two potential treatments i.e. which return the nano-needle response to normal - SS-31 and copalone. SS-31 has completed the patient treatment bit of a Phase 3 trial for use in a rare genetic (metabolic) disease; however, I think the report etc. wont be out until December 2020. Then there's the issue of using SS-31 in another disease i.e. ME - outside my knowledge.

 

[Rufous McKinney]

Then there's the issue of using it another disease i.e. ME - outside my knowledge.

Here, with US Supplemental Medicare Policy: it seems that would be declared Off Label, and they don't cover it. So if you can get an RX from a doctor, you can pay with your own money, presumably.

I tried to discuss this with my insurance representative. That "failed".

 

[Pondering]

Check out Ron Davis talk at last month's NIH Conference. Ron mentions two potential treatments i.e. which return the nano-needle response to normal - SS-31 and copalone. SS-31 has completed the patient treatment bit of a Phase 3 trial for use in a rare genetic (metabolic) disease; however, I think the report etc. wont be out until December 2020. Then there's the issue of using SS-31 in another disease i.e. ME - outside my knowledge.

I can't find a "copalone"? Did he mean copaxone? That is used to treat MS (according to google/bing). https://en.wikipedia.org/wiki/Glatiramer_acetate

 

[Rufous McKinney]

the nano-needle response to normal - SS-31

Here is a bit of background on mitochrondria and SS-31

https://jasn.asnjournals.org/content/18/1/213

Mitochondrial Targeting with Antioxidant Peptide SS-31 Prevents Mitochondrial Depolarization, Reduces Islet Cell Apoptosis, Increases Islet Cell Yield, and Improves Posttransplantation Function

 

[FMMM1]

I can't find a "copalone"? Did he mean copaxone? That is used to treat MS (according to google/bing). https://en.wikipedia.org/wiki/Glatiramer_acetate

Yes. My spelling is poor and I often just write out my thoughts without checking on the web - as in this case.

I referred you to Ron Davis's talk at the recent NIH Conference [April 2019]. Copaxone returns the nano-needle test to normal.

I think some of the recent findings e.g. Bhupresh Prusty's, i.e. mitochondrial fragmentation (talk before Ron's), and the nano-needle will redefine some illnesses e.g. MS. I will not be surprised if some MS drugs, or other drugs, have potential in ME. To me part of the problem is what is ME -- MS? MS, to me, isn't that well understood/easily diagnosed. Then there's Lyme disease --- fibro --

 

[kms1990]

Check out Ron Davis talk at last month's NIH Conference. Ron mentions two potential treatments i.e. which return the nano-needle response to normal - SS-31 and copalone. SS-31 has completed the patient treatment bit of a Phase 3 trial for use in a rare genetic (metabolic) disease; however, I think the report etc. wont be out until December 2020. Then there's the issue of using SS-31 in another disease i.e. ME - outside my knowledge.

Very intersting. I cannot wait to find out more about these trials. It seems like they are onto something serious here

 

[FMMM1]

Very intersting. I cannot wait to find out more about these trials. It seems like they are onto something serious here

I'm not clear how access to SS-31 would apply i.e. if you have ME. Similarly copaxone.

 

[Wally]

Here is another study about exosomes and their effect on the brain. While not a study about ME or CSF and it is a study related specifically to brain development and brain disorders, it does seem to provide some additional insight into how these little exosome parcels could reveal additional clues related to the neurological dysfunction seen in M.E., CFS and similar neuro-infammatory illnesses.

https://www.sciencedaily.com/releases/2019/07/190722132448.htm

Exosomes may hold the answer to treating, diagnosing developmental brain disorders
New discovery suggests cellular 'cargo' transporters play a profound role in creating brain cells and circuits
Date:
July 22, 2019
Source:
Scripps Research Institute
Summary:
Scientists shed new light on the role that exosomes play in brain development. They show that exosomes are not only integral to the development of neurons and neural circuits, but they can restore health to brain cells affected by developmental disease.

Like overpacked suitcases unloaded from the underbelly of a jet, molecular satchels called exosomes are continuously deployed from all cells in the body -- each one brimming with an assortment of contents that another cell may unpack and use. By sending off these biological parcels, cells communicate with each other via shared proteins and genetic material. . . .

They also injected healthy exosomes into a mouse hippocampus -- a brain region involved in learning and memory -- and observed increased neuron proliferation. This in vivo facet of the study proved that the exosome bioactivity seen in cell cultures carried over to an animal model.

Armed with their remarkable findings, Cline and her team now intend to dig deeper into their results and explore a slew of new questions related to exosome bioactivity and potential clinical applications: Could exosomes be measured in a blood test to detect disease or treatment efficacy? Do these findings also apply to autism spectrum disorders (ASDs) and other neurodevelopmental diseases, such as Fragile X? Could exosome-based therapies one day help patients with brain disorders? . . .

See, Exosomes regulate neurogenesis and circuit assembly. Proceedings of the National Academy of Sciences, 2019; 201902513 DOI: 10.1073/pnas.1902513116