Discussion in 'ME/CFS research' started by butter., Jun 4, 2020.
A factor in the blood might have rapid turnover - maybe a half-life of six hours. By the time plasma exchange is over the factor is replenished. Plasma exchange is designed to remove molecules with half-lives of months-like antibodies - which as potential signalling molecules are very unusual this respect.
The experiments seem to suggest that the blood factor has an effect on cells for a day or even several days.
I'm just realizing it's not actually clear that the effect persisted for six days. That was the duration of the experiment, but did the effect last this long?
Here however the effect persists and seems not to diminish over time.
My understanding seems opposed to what has so far been posted.
If there is something in the blood then it must have got there somehow.
The something in the blood seems to be what is causing a problem in pwME cells - so in order to function 'normally' then that something in the blood needs to be absent, as in not present.
My understanding is that a few 'tests' have been conducted to establish that a healthy cell in plasma from a pwME behave like pwME cells, and that pwME cells in 'normal' plasma behave like 'normal' cells.
Hence the origin of the hypothesis.
If plasma exchange of 'normal' plasma into a pwME isn't working then it seems, to me, that this could be for a couple of reasons;
Whatever made the 'something in the blood' is still making it, so 'contaminating' the fresh plasma or
The universe hates us or
Option C (yet to be determined/remembered)
To hear this from you sir, is very good news for me! So what factor would theoretically be responsible? Virus rna?
So it changed something for good potentially?
I'd say also that, if there is an "X" factor in the blood and you remove it, even if the cells instantly return to a normal state, the symptoms may not also clear up instantly. Damage and dysregulation may have occurred and may need some time to "heal" before returning to normal. During that interval, the "X" factor may build back up again.
So why isn‘t the whole world not looking for it? I mean there is a huge financial benefit to find this out!
In a cell culture system there is no clearance route like liver or kidney which may control a short half life.
Why is it so complicated to identify this? Could you give me some kind of insight into that?
There are quite a few "chemicals" circulating in our blood, and many of them are in incredibly small quantities.
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.
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'.
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.
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.
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.
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.
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.
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.
Separate names with a comma.