Plasma exchange

[lunarainbows]

There are quite a few "chemicals" circulating in our blood, and many of them are in incredibly small quantities.
https://www.sciencedaily.com/releases/2011/02/110224145609.htm
If you don't know what you are looking for, and if the unknown chemical only differs slightly from "normal" chemicals, that would make it so much harder.

It baffles me though. When we are so ill,.. How is it that no one has been able to find what is wrong with us yet? Lots of people are doing research on us. We first heard about the something in the blood quite a few years ago and it seems we are still not closer to finding out what it is despite coming at it from so many different angles.

ive read so many blog posts on the different findings or new research angles and each time I get excited about it but then it ends up being false hope or I get disappointed. I just don’t understand why it’s been so hard to figure this out, when the level of our physical and cognitive function is scarily low. There are so many other chronic conditions, Often much milder even than severe ME, which science has been able to figure out, or find treatments for, yet for some reason can’t figure out for ME why?

we have lots of things wrong with us that are quite unique and rare, like the severe noise and light sensitivity (as far as I’m aware only really found in autism, dementia (?), certain types of brain injuries, migraines and other head related issues, and even then often nowhere near the level of sensitivity we experience), and the severity of level of functioning like inability to sit upright or hold head upright - I do not know any other condition which this happens to except ME, (Even in PoTS by itself, once it’s treated, they are then very often able to go about their lives), which I thought would have helped science to figure things out too.

 

[Trish]

I think the answer is twofold:

- Biology. Incredibly complex, with many thousands of different chemicals in the blood.

- Money. ME research is starved of funding. For example Karl Morton wants to research L-form bacteria to see if they might be related to the 'something in the blood', but has had his bids for funding turned down and is now crowdfunding. Other teams with interesting ideas for research are getting by on tiny grants from ME charities.

Edit: Corrected 'not' to 'now'.

 

[lunarainbows]

Do we know how much Karl Morten has raised yet? That crowdfunding page doesn’t say how much he has raised so far or how much more he needs to get to target.

 

[Hutan]

I think the answer is twofold:

- Biology. Incredibly complex, with many thousands of different chemicals in the blood.

- Money. ME research is starved of funding. For example Karl Morton wants to research L-form bacteria to see if they might be related to the 'something in the blood', but has had his bids for funding turned down and is now crowdfunding. Other teams with interesting ideas for research are getting by on tiny grants from ME charities.

I think too that a lot of ME/CFS research is not very good, or at least doesn't tell us much. Some of that is due to money (e.g. the very small sample sizes and the pilot trials that don't progress to RCTs). But we are still seeing research proposed for the very scarce amount of funding that has subjective outcomes with unblinded treatments. Projects with CBT and projects aiming to identify personality flaws are still funded. We still see the Chalder Fatigue Questionnaire. And repeated measurements of peripheral blood cytokines are being made - as if measuring them one more time will at last find something significant because, you know, 'there's inflammation' - and they are fairly easy to measure. And still, poor patient selection.

I think, until recently, a lot of the scientists involved haven't been the best, because, until recently, if you had the ability to study almost anything else, it was a much smarter decision to go and do that. And knowledge was lost because funding ran out and small studies never got published and researchers moved onto other things in order to feed their families and keep their labs functioning. Some of the techniques and technologies that may well give us answers eventually are quite new and there's still quite a lot of fine-tuning to do to make things work properly.

I was looking at a supplementary table of molecules identified in the cerebral spinal fluid of people with ME/CFS and healthy controls the other day and the list of molecules with quite different levels was long - and even then, many of the rows were groups of molecules. There's lots to be looked at yet. It's such a shame that much of the past research and even the current research does the same thing (that isn't helpful) over and over again.

I agree with you though Luna, when I'm in a crash and I feel so bad, it really is hard to believe that there is not something blindingly obvious to find, something major to explain such an effect.

 

[Graham]

I agree with you though Luna, when I'm in a crash and I feel so bad, it really is hard to believe that there is not something blindingly obvious to find, something major to explain such an effect.

I tend to work more with analogies when I want to get my brain around something, and to me the search for the rogue trigger (the missing chemical) could be compared with a search, in America, for a lone, serial murderer. Crucial factors are the abilities of different police forces to fund an investigation, the qualities of any investigative team, the extent to which different police force co-operate with each other and share evidence, the ability to actually make a correct selection of that one murderer's victims (i.e. an appropriate set of criteria to select people with ME), all with the realisation that there might in fact be half-a-dozen separate, but "related" serial murderers.

I keep quoting the fact that the total amount of money spent on biomedical research into ME over the last 40 years is roughly the same as the amount currently spent in one week on research into HIV/AIDS. @Dolphin , who is a much better mathematician than me, thinks a fortnight is a safer "quote", but that's just our pedantic nature! What is amazing is that so much progress has been made with so little funding.

 

[butter.]

Personally I tend to believe that we would have found the cause of it already if it could be found with current science/knowledge/technology.

I believe one day the answers will be found in the big black boxes of medical science like „mitochondria“ and „brain“.

I hope sooner than later.

 

[Badpack]

Well you could start with using Cfs blood and run it through a filter of different kDalton sizes to got closer to what you are searching for. Imo even this hasn't happened yet, what lets me think, none of the other scientists believes in the something in the blood tbh. We have 3 different possible cell culture tests right now. Ron Davis - Nano needle, Alain Moreau with his own nano needle like devise and Bupesh Prusty with his mitochondria experiment. The only one i hear news from now and then is Prusty, the others kinda just dropped their blood work. So not sure what to think about all of this.
Its also hard to believe after 7 plasmapheresis that something magical is still in your blood that makes you this sick. Possible, sure. But seems pretty unlikely. Either its produced that rapidly or it comes back to fast that your body cant recover. My favorite theory for now is still SS31 which worked in Rons nano needle, which also explains Prustys fragmented mitochondria. So following this, it could be a virus particle (assumed by Prusty), which could be produced by all body cells or white blood cells. If the white blood cells are the producers, it would explain why some can (partially) recover with Retuximab/Cyclo. and why its back so fast in the bloodstream.
But my guess is as good as yours, so im all ears.

 

[Mithriel]

There has been lots of interesting results over the years but they all fade away with no funding, like the cardiac problems found by the NIH but then .... nothing for 20 years.

ME is so widespread that it must be caused by something going wrong with basic biology. The cells and systems work when not much is demanded of them but when they are called into action they just can't do it.

I think of it like the difference between 2 people going to work and finding the lift isn't working so they have to climb 10 floors. The guy who just parked his car manages fine but the other who has just jogged 5 miles will struggle.

It is also possible that much of what we experience is a protective effect. Paul Cheney speculated that diastolic dysfunction causes us to lie down to protect the heart.

 

[Badpack]

@Mithriel ever seen an older person with a heart condition ? Ive seen so many ppl with NYHA 4, global heart failure. They would outrun me everyday. A diastolic dysfunction is maybe a side symptom that worsen things but by far is anything profound in Cfs.

 

[Mithriel]

When heart issues were being looked at in ME, Paul Cheney examined all his patients and found that they all had diastolic heart failure, which makes sense as that is an active process and could well be involved with the problems found by Workwell.

He was interested as he had systolic heart failure and had to have a heart transplant. He speculated why his heart had given out while his patients' hearts did not and decided that his heart failed in the background so he carried on overloading it till it failed completely but in his patients they became fatigued so rested their hearts.

I use a heart rate monitor and am not alone in finding that when I am in particularly bad PEM my heart rate drops drastically. I also see the effect with my blood pressure when my diastolic becomes very low (<50).

People with ME have been known to die from heart attacks when they exercise too much - an MP died in the House of Commons gym - and it was seen as a problem 40 years ago, but heart issues are one of the neglected areas because of the dubious concentration on fatigue.

Many people with ME have small hearts, can't remember the details but we are not like other heart patients, the heart is not damaged just not working the same as everything else in ME.

 

[wigglethemouse]

I think there are subsets who will respond differently. Systrom/Oaklander believe there is a small fiber neuropathy subset (based on skin biopsy) where whatever has gone wrong in the biological process has damaged nerve fibers. So if you are in a subset where there is physical damage, it is going to be a long process to repair that damage when the "factor in the blood" is removed. They associate SFN with impaired cardiac return and hypoxia.

Statement in abstract from Oaklander about SFN, hypoxia, and impaired cardiac return.

Internal symptoms also reflect premature hypoxia and impaired cardiac return from malfunctioning sympathomotor blood-vessel regulation.

Source : Chapter 10 - Dysimmune small fiber neuropathies - 1 May 2020

 

[lunarainbows]

I think there are subsets who will respond differently. Systrom/Oaklander believe there is a small fiber neuropathy subset (based on skin biopsy) where whatever has gone wrong in the biological process has damaged nerve fibers. So if you are in a subset where there is physical damage, it is going to be a long process to repair that damage when the "factor in the blood" is removed. They associate SFN with impaired cardiac return and hypoxia.

Statement in abstract from Oaklander about SFN, hypoxia, and impaired cardiac return.

Source : Chapter 10 - Dysimmune small fiber neuropathies - 1 May 2020

I think we’ve had other studies showing hypoxia in the brain even in the absence of PoTS (30% drop in oxygen compared to controls if I remember correctly?). Is there no treatment that already exists, for this type of issue?

So is the hypothesis that there’s a problem with the blood vessels and so there’s less oxygen - in that case is it a problem with blood vessel constriction? But wouldn’t that cause in all cases continuous high blood pressure (Isn’t that what high blood pressure is - vessel constriction)?