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A few theories based on recent findings

Murph

:)
Messages
1,799
The ratio of theory to data on this disease is huge! Sometimes it seems a little comical how often we sift the few facts we have for a new angle.

But I get it. It feels very positive. And for each new person being afflicted/diagnosed, moving through the available information to get (as close as their capacities will permit to) a cutting-edge understanding is a very real process of exciting discovery. (I did a deep dive and exploration process myself within the last year which I found very useful, and I can see my capacities are lower than those of @AdamS !)

But it is not just self-education or amusement. Reseachers (and their spouses!) are involved in this forum and a good theory can make its way back into the system to be tested. So I feel all our theory-making has potential.

What will be truly exciting, however, is when there are so many papers that lay person theory-making can't keep up...
 
Messages
516
But it is not just self-education or amusement. Reseachers (and their spouses!) are involved in this forum and a good theory can make its way back into the system to be tested. So I feel all our theory-making has potential.
I don't know what anyone else is in it for, but by far the biggest reason I'm doing this (just short of only) is finding real solutions for disease management, that don't expire after a couple months, mostly via reversing downstream effects. Which make them opposite goals - couldn't expect researchers to have much use for most of what I write even if they weren't already aware of it.
 

AdamS

Senior Member
Messages
339
@alicec These aren't my categories. I was simply trying to show all/most of the key contents of human serum at a high level in graphical form to aid discussion. :)

My comment about antigens should be taken as complete speculation but as you probably already know, an antigen is just a unique molecule of a harmful agent. Antigens are capable of impeding biological processes causing disease when binding. Antibodies (which are large Y shaped proteins) usually rely on antigens and are secreted by B cells...we know a fair bit about the relevance of B cells due to the Rituximab trials so it's not actually that crazy to link these things together and suggest that it is an autoimmune type disease in a subset.

Anyway, i'm no expert and certainly don't know the answer!
 

alicec

Senior Member
Messages
1,572
Location
Australia
Of course the large molecule/protein could be a carrier for something smaller?

It's possible though if that were the case one would expect to find the active factor in both the small and the large fraction after filtration.

This is because carrier proteins don't bind the molecule which they are carrying very tightly. They need to be able to release the substance easily when it is needed.

Filtration would change the binding equilibrium and at least some of the small molecule would be likely to be released.
 
Messages
1,478
It's possible though if that were the case one would expect to find the active factor in both the small and the large fraction after filtration.

This is because carrier proteins don't bind the molecule which they are carrying very tightly. They need to be able to release the substance easily when it is needed.

Filtration would change the binding equilibrium and at least some of the small molecule would be likely to be released.
Yes probably .....it will be interesting to find out what it is after all this speculation. :)
 

alicec

Senior Member
Messages
1,572
Location
Australia
These aren't my categories

Well many others, including myself, would categorise differently. Many things are missing from your scheme and some are doubled up.

an antigen is just a unique molecule of a harmful agent.

As the name implies, an antigen is a substance which causes an immune system to produce an antibody against it - ie it generates antibodies. Usually, though not always, an antigen is an immunogen - ie it generates an immune response (activation of T cells by antigen-presenting cells; some small molecules can't do this alone).

The antigen-antibody interaction is highly specific - each antigen has it's own antibody. We are making different antibodies all the time and they are recognising and disposing of their respective antigens all they time. This is the normal protective function of the adaptive immune response.

I am trying to understand what aspect of antigen-antibody interaction you think becomes problematic in ME/CFS.

You are saying that an antigen is the trigger for the cascade that leads to this illness. This implies that either:-

the problem lies with the response elicited to a particular antigen - hence my question, do you think everyone with the disease has been exposed to this particular antigen?

or

the problem is not peculiar to the antigen but lies in aspects of antibody-antigen interaction to any or a number of antigens.

I'm not aware of any evidence for the latter proposition, apart from the subset who may be producing problematic auto-antibodies. The latter is a special case and in any case is a consequence of B cell function and how self-reactive clones are eliminated, not something generated by antigens.

What do you mean?
 
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Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
Cut him some slack Alice.. :)

There are many theories around at the moment, but quite importantly; almost none of the findings that the theories are based on have been independently replicated. That`s a huge problem. Ron davis` fast track approach gets me hopeful, its the right way to approach it, or it would take decades..

Any idea is as good as the other at this point. Could be different diseases, could also be unknown mechanisms at work!
 
Messages
67
Location
Spain
@AdamS So nice work. If you don´t mind it, i have traslated the graphics as well as some of your explanations and post it to the spanish EM community forum where it has been also kindly appreciate.

Congrats for that job!!!
 

gregh286

Senior Member
Messages
976
Location
Londonderry, Northern Ireland.
Hi all, like many of us on here I read quite a lot about ME, mainly because I want to solve it, get better and go for a pint with all of you great people when i'm well! :D

I decided to map out a few theories based on what i've been reading about energy metabolism over the past few weeks/months, I don't expect much of this to be new to you, but i've added my own spin on a few of the theories...hopefully it gets us talking and thinking of new ideas :thumbsup: All comments, criticism and ideas welcome!

wu12xk.jpg


EDIT: I've also created a map of common serum contents, if it's the case as Davis, Fluge & Mella say that the problem is in ME/CFS patients' serum, then these are the areas we need to be searching.

t5rcs0.jpg


Cheers, Adam


4.
Only because i can trigger it if i want to. I can "force" on a cell danger response.
Patterns in amino acid studies also support the theory of alternative fuels.
Quite a few do well on high dose aminos in crashes, myself included.
 
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GreyOwl

Dx: strong belief system, avoidance, hypervigilant
Messages
266
I liked this diagram, is it helpful:
 

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AdamS

Senior Member
Messages
339
Well many others, including myself, would categorise differently. Many things are missing from your scheme and some are doubled up.

The categories of serum contents are taken from Wikipedia. I just put them into a graphic. Maybe I should have have added the source in there too. I tell you what, why don't you make a graphic with your improved categories and post it if it makes you feel better. :)

What do you mean?

I don't know anymore, on reflection it was a comment made without enough research. I'm going to leave it to the experts from now on. Great job for calling me out on it, i'd be interested to know your opinion about ME triggers/mechanism as you seem to have a better understanding than I do.
 
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alicec

Senior Member
Messages
1,572
Location
Australia
The categories of serum contents are taken from Wikipedia

Wikipedia is as good as the understanding of the person writing the article, in this case not particularly helpful.

Actually I'm sorry I diverted things by discussing this classification and I apologise. Really it is irrelevant. We just need to understand that serum is an immensely complex fluid. Each of the broad categories, however they are defined, contains many thousands of substances.

I can't see the point of people on this forum speculating about what it is in serum that is causing the effects that Davis and Fluge and Mella have observed. Davis has said the molecule is large, probably a protein. Our trying to guess what that protein might be is just a waste of our limited energy resources.

The scientists involved fully appreciate the complexity they are dealing with and have the considerable technical resources which will be needed to isolate and characterise the substance(s) having the effect - ie find the proverbial needle in the haystack.

Most importantly, Davis has come up with an ingenious assay which will enable them to rapidly assay what could turn out to be millions samples as they fractionate and sub-frationate serum in order to track down this factor(s).

I'm happy to leave them to it.
 

alicec

Senior Member
Messages
1,572
Location
Australia
i'd be interested to know your opinion about ME triggers/mechanism

We don't have nearly enough information yet to propose detailed mechanisms.

The scientists of course are well aware of this and are trying to do more definitive studies.

Several recent studies have focussed on different aspects of defective energy metabolism. I haven't seen anything yet that suggests that the different defects are not broadly compatible, that they couldn't be part of the same mechanism.

In any case, Davis and Fluge and Mella have independently confirmed that a factor(s) in patient's serum is affecting the energy response of cells. Once removed from this serum, cells from patients and controls behave in the same way.

This suggests that the energy defects are downstream events. They may be important in mediating symptoms but the fundamental problem lies further upstream.

What is leading to production of this serum factor(s)? Knowing what the substance is could give important clues and will undoubtedly lead to a new set of hypotheses that will take us further back along the triggering pathway. At this point we have no idea what this could be.

As for the ultimate triggers, Naviaux has added an important new concept, namely the cell danger response, as a way of unifying a variety of possible initial triggers (both infectious agents and various environmental insults). Everyone responds to these initial triggers with a CDR, but in ME/CFS patients the CDR does not resolve. What is the fundamental defect behind this failure?

Presumably this is what his current research is focussed on and is something we can all eagerly await. Again we have little idea yet what this could be.

Does this defect lead to production of the mysterious serum factor or are there more layers of complexity here? Impossible to say yet.

Finally there is the likely autoimmune subgroup that Fluge an Mella have brought back into focus. Their Rituximab studies clearly show that there is a group of patients whose likely fundamental defect lies in the immune system. If it is not a strictly autoimmune process then at least there is some fundamental problem of antibody production by B cells.

Are these an entirely separate group? Probably not. Perhaps the starting mechanism is different but these patients seemed to share the same energy defects.

So there are still many gaps in knowledge but there has never been a more exciting time in research. In the not too distant future there is every reason to expect that many of these gaps will be filled.
 

AdamS

Senior Member
Messages
339
@alicec

Some really good points which I take on board, thanks for your input! I eagerly await the next findings and feel very fortunate that we have such great researchers working hard every day to help ME patients.
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
In Dr Byron Hyde's definition of ME, he writes:
The Central Nervous System (CNS) symptoms, as well as the clinical and technological abnormalities, are caused by a diffuse and measurable injury to the vascular system of the Central Nervous System. These changes in the organization of the CNS are caused by a combined infectious and immunological injury and their resulting effect on CNS metabolism and control mechanisms

A significant number of the initial and long-term peripheral or body symptoms, as well as clinical and technological body abnormalities in the M.E. patient, are caused by variable changes in the peripheral and CNS vascular system. The vascular system is perhaps the largest of the body’s organs and both its normal and patho-physiological functions are in direct relationship to CNS and peripheral vascular health or injury, to CNS control mechanisms and to the difficulty of the peripheral vascular system and organs to respond to CNS neuro-endocrine and other chemical and neurological stimuli in a predictable homeostatic fashion.

I wonder how this can be squared with Dr Davis' finding that the ongoing disease cause is "something in the serum."
 

lansbergen

Senior Member
Messages
2,512
Everyone responds to these initial triggers with a CDR, but in ME/CFS patients the CDR does not resolve. What is the fundamental defect behind this failure?

The agent is very difficult to destroy and the response keeps going on and on?
 

sorin

Senior Member
Messages
345
ME/CFS might be a mix of different diseases that have in common substantial impairment of energy production.
It is NOT ONLY about energy, is also about neurological damage, immunity, cognitive damage, dermatological problems, and many many more... It also affects the brain in that you can not enjoy anymore many things that you used to enjoy earlier...
 

adreno

PR activist
Messages
4,841
It is NOT ONLY about energy, is also about neurological damage, immunity, cognitive damage, dermatological problems, and many many more... It also affects the brain in that you can not enjoy anymore many things that you used to enjoy earlier...
All of which can be explained by a lack of energy.