Blog: 'Summary so far of "Something in the blood"' by Simon McGrath

This mission sounds tailor-made for ME/CFS research into a biomarker! Someone with scientific credibility and/or advocacy group backing should reach out to them to try to interest them in the disease. I know Sadie Whitaker of SMCI said that exploratory drug company research is where a lot of discoveries get made. Is she on this forum? It would be amazing if she could reach out to them!

 

and IGGs are derived from human blood
very small risk of viral infection, since its 95% cleaned, they say

 

I've been on rivaroxaban - Xaralto - for almost three years after 10 years on Coumadin after unprovoked bilateral pulmonary emboli in 2006 (it was my second PE; the first was provoked by knee and ankle surgery in 1998). It has done nothing for my ME. That said, when I had the PE in 2006, I was prescribed Lovenox, i.e. Heparin, and the period I was on it did correlate with a marked improvement in my symptoms. I've always thought the improvement was more likely due to all the IV fluids they gave me in the ER (they needed to do a second CT scan so gave me the fluids so I'd pee out the radioactive dye from the first CT scan). But the improvement lasted about 10-14 days, which was the same period on which I was on the Lovenox shots. I know there have been some ME patients over the years (early to mid 2000s) who swear to God that Heparin makes them feel better. I've always been skeptical but agnostic about this claim. ::shrug:: Who knows?

Thanks, @Simon M for the review. Something hopeful for the time-being.

 

I decided to just go ahead and email SMCI / Sadie Whitaker about this, since she fits both categories and has lots of experience in the pharma/biotech world. I hope something comes of it! Thanks to @junkcrap50 for posting about the exosome adsorption company, and to others for the interesting discussion.

 

No problem. The credit belongs to @Joy&K0$ on PR. I think it's perfect tech for us. I think we as patients should also reach out to them too. Let them know that Ron Davis and Dr. Prusty might be interested in it too.

 

As I understood the results were promising; indeed, I was told some were much better even 1 year after immunoadsorption (plus IGG). But they restricted their study to participants that showed autoimmunity, and they told me if there are no autoimmune hints it's not indicated and won't, most probably, help.
I am not sure if there will be a follow-up study because of lack of money.

 

Yep, count me in too. I had a blood test that lasted 1.5 hours (they were injecting me with a hormone to see my hypothalamus response, i think its called TRH test) and injected me with heparin to avoid the blood from clotting. I felt amazingly well for 2 days and then the effect faded away.

Edit : I also recall mentioning how well i felt to my endocrinologist who dismissed me outright saying that this kind of test had nothing to do with my amelioration of symptoms.

 

One thing that's slightly bugging me here. A virus (and as Bhupesh Prusty said potentially bacteria) can use mitochondrial fragmentation to evade the immune system. If we don't have a viral infection then why would our cells fragment the mitochondria? Surely if our cells identified a threat (e.g. increased bacterial translocation from the gut - leaky gut) then they would attempt to increase the immune response not dampen it down. I vaguely think Bhupesh dealt with this; however, I'd be grateful if someone would explain.
Is Bhupesh suggesting that there are some infected cells (viral/bacterial) and these are signalling nearby cells (microRNAs in exosomes) i.e. causing the observed mitochondrial fragmentation? Wouldn't a viral infection turn up in the blood stream (tests for viral RNA/DNA)?

Regardless of the explanation I think this is very interesting finding. I assume that identifying microRNAs in exosomes shouldn't pose too many difficulties for a leading research group e.g. using mass spectrometry.

Can the measurement of surface area of mitochondria (fragmentation) be used as a diagnostic test e.g. by measuring the surface area with unfiltered/filtered plasma?

One final thought. I recall a reference to impaired calcium signalling in Bhupesh's talk; reminds me of the Australian research on TRIP receptors.

 

Maybe it doesn't make sense because we're trying to understand it from either the "autoimmune" or the "infection" angle but it is neither of those, but something else that nobody has really considered. Every known disease mechanism was once unknown. That researchers are having so much difficulty figuring out the mechanism in ME/CFS could be an indication that there is a new kind of mechanism to discover.

 

Prions???

 

Coz it's Tuesday?

 

- ROS, oxidative stress
- "drugs and starvation" (anti-toxoplasma drugs cause mito fragment in parasite)

 

I came across this after posting/before reading your replies and yes it refers to something new to me (at least) i.e. prions. From:
https://www.frontiersin.org/articles/10.3389/fnins.2017.00026/full


"Multiple Sclerosis and Inflammation

Inflammation is a central player in most neurodegenerative diseases. Neuroinflammatory processes exert profound changes not only in the vicinity but beyond the local environment of cells. In addition to the propagation of toxic proteins, exosomes also carry important inflammatory modulators, such as mRNAs, miRNAs, and cytokines (Gupta and Pulliam, 2014). Microglia, the resident macrophages of the CNS, can shed exosomes loaded with pro-inflammatory molecules such as IL-1β (Bianco et al., 2005) and other cytokines. Their scavenging functions are also crucial in the clearance of toxic seeds such as Aβ (Yuyama et al., 2012). Furthermore, endocrine signals from hematopoietic cells directed to the brain can be transported by exosomes, a phenomenon that is augmented in a context of inflammation (Ridder et al., 2014). It is interesting to note that extracellular vesicles can readily cross the blood brain barrier, adding a communication channel by which systemic inflammation can modulate physiological processes in the CNS."

Second extract:
"As many other proteins are present in exosomes, recent initiatives have used large-scale methodologies to analyze exosome content. Using mass-spectrometry to analyze circulating microvesicles, it was identified that PD patient fibroblasts are enriched in syntenin 1, a regulator of exosome biogenesis (Tomlinson et al., 2015). Similarly, a set of nine miRNAs have been shown to be distinct in exosomes purified from control and prion-infected cells (Bellingham et al., 2012a), defining a molecular “signature” that can identify a pathological process. Although the relevance of such hits in the disease is not established yet, these approaches suggest that establishing a “bar-code” from the exosomal profile of patients might be a more valuable diagnostic tool than quantifying specific disease-related proteins, which are often mixed at early disease stages."

@Wonko - good reply!

 

It sure is. Interesting.

 

perhaps its them that cause homeopathic medication to work?
since it makes particles small enough?

if some hyper-diluted (shaken, stirred ...) herb/mineral/ may be able to access/hike on exosome vehicles, it could explain why homeopathic things function.

another line of communication and transport, and perhaps "attack" (angle, strategy, target) as well.

 

I think you are being generous Trish. A good homeopathic dilution is just water, no molecules of the active ingredient at all.
From https://rationalwiki.org/wiki/Homeopathy

 

I think that is indeed what Prusty was suggesting-- that a very small number of cells was infected (not enough to create a significant difference in the concentration of blood particles between controls and pwME), but those cells were actively putting out signals via exosomes that spread the mito response to all (or many more) of the cells. Not sure if the difference from the controls was that there were any infected cells or that the infected cells were doing different things in pwME than in the controls, but I think it was the former. This is all from memory though, so I could be off base. I do remember he skimmed over a lot of intermediate explanatory steps with things like "this is really complicated and I don't have time to explain it here," so we may just have to wait for the publication of his findings, which I'm very eager to read!