Discussion in 'Health News and Research unrelated to ME/CFS' started by Andy, Nov 30, 2017.
Full text at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504148/
Thanks for posting.
Dosage is an issue.
My daughter is on 0.07 mg
Yes, a tiny dose,even though she is an adult.
But she couldn't tolerate higher doses.
So, the question is : at what dose does this work?
Dr Chia, and others, recommend it too.
The dose is individual, and it´s also depending on genetics, if it works or not, according to my doctor.
I think it is unlikely that any potential benefit of naltrexone has anything to do with these cytokines since they are not raised in ME/CFS. (Nor is the body's own 'bioassay' for them in the form of CRP.) We have pretty extensive evidence that ME/CFS is not 'inflammatory' in that sense.
What about naltrexone binding to TLR4? Can you think of ways that signalling through this pathway could be relevant to ME/CFS?
An interesting thought. TLR4, as you probably know, is part of a receptor complex that confused us for about twenty years before it was finally worked out which bits did what. If ME/CFS involved some sort of 'decoy' signal that managed to make people feel ill as if they were making TNF and IL-6 but actually bypassed those molecules then yes, a drug that slotted in to the complex might have such an effect. Maybe it would be an effect specifically within the brain or something, too. I don't know enough to suggest anything more specific but I think such a scenario is very possible.
If ME symptoms involve innate immune activation, that might be happening for a reason e.g. a compromised adaptive response.
If you jam innate immunity dont you risk worse infections?
@Jonathan Edwards, I’ve asked this question before but you didn’t reply and I’m very interested to understand:
Does the Mark Davis/Montoya cytokines study not provide evidence of inflammation?
Montoya is quoted as saying: “Now that the study has established that it’s inflammatory, we can look for those drugs that treat inflammation” (http://scopeblog.stanford.edu/2017/11/08/demystifying-chronic-fatigue-syndrome/?linkId=44501684)
Please can you explain where you disagree with Montoya?
Because I think he is oversimplifying, or simply wrong, I am afraid. I spent my entire career working on inflammatory effector mechanisms. To say something is inflammatory you need some evidence of actual inflammation and in ME there is none. Moreover, the standard cytokine mediators of inflammation do not appear to be operating - as indicted by the normal CRP. Drugs that treat inflammation have already been tried, whether steroids, anti-inflammatory analgesics or TNF inhibitors. They are not useful. A useful analysis has to be much more specific.
Thank you Dr Edwards for your clarification. Then may I ask: do you have any ideas of what might be wrong. Have you any theories? Speculations?
Last night on CBC radio I heard an interview with one of the Canadian AIDs doctors who was influential in developing the AIDS cocktail. Because of the urgency of the AIDS crises, he said at one point, that "corners were cut" in order to get a treatment out. He didn't specify. The Interviewer didn't ask. Why isnt there a similar urgency here? I know folks don't die, but it's a living death.
I know I'm getting off topic somewhat.
I have speculations but nothing concrete enough to offer publicly.
It is possible to 'cut corners' if you know what direction you are heading, like knowing there is a retrovirus to get rid of. But if you have no real idea which way to head then it makes no sense. Much of the problem with ME research has been that people have pushed forward with handing out treatments without proper trials and wasted a lot of time and money doing so. [/QUOTE]
Interesting. Have you discussed this with Montoya or Davis? I’d be very interested to know their response, and to understand to what extent you disagree. I would be very concerned if Montoya is making statements about the nature of ME/CFS which are not supported by evidence. Given the divide between BPS and non-BPS researchers, it is particularly unfortunate if/when people on our side make false claims, as the debunking of such claims is frequently used to discredit valid opposition to the BPS “model”.
Out of interest, do you have similar doubts about the recent research by Prof Ed Bullmore and others linking depression to inflammation? (eg http://www.telegraph.co.uk/science/...ical-illness-could-treated-anti-inflammatory/)
If only more people would show similar restraint.
(Edited to add second quote)
I have not met Dr Montoya or Dr Davis.
I think you raise reasonable concerns about false claims. There have been far too many of these in the 'non-BPS' camp over recent years unfortunately.
Judging by the media piece on Bullimore you linked to he is grossly oversimplifying, yes. Unfortunately, this is the norm in medical science now - which may be why not much progress has been made in the last fifteen years as compared to the previous forty. I am not sure what the problem is but I suspect it is not having a wide enough training. Most people in immunology have no training in histopathology now, for instance. But unless you understand the architecture of cell responses in tissues you are pretty guaranteed to draw false conclusions from findings in laboratory flasks or blots. The action of complement one side of a blood vessel is the complete opposite of its action the other side of a blood vessel for instance.
If, as you go on to say, immunologists don't have a sufficiently broad training in their discipline, then I despair a bit that we will reach an in-depth understanding of the contribution of immunological defects to ME/CFS anytime soon.
I've always thought the reason for the immunological over-simplification that seems to have become almost the norm is that immunology is just so difficult and dependent on mastery of a lot of detail.
At least that's how I have always found the subject. My original training was in biochemistry but since a lot of my working life was spent in search of a function for a novel protein I had purified, I had to become familiar with a lot of other disciplines in order to put the protein to the test.
I was quite confident that I grasped a sufficient understanding of a number of these disciplines to know how to proceed but not so with immunology. There were just too many pitfalls for the uninitiated.
I've imagined that much of the problem with the oversimplifications you refer to is because the people making them are not immunologists and don't fully understand what they are dealing with.
Of course there are immunologists and immunologists and I realise one needs to discriminate between which variety is speaking. Still if as you say their training in general is inadequate, who is there to rely on to get to the bottom of the immunology of ME/CFS? Are we going to be floundering for another 15 years?
Reasonable concerns but I would be a bit more optimistic, based on my experience in RA.
In reality it is the immunologists themselves who are most guilty of oversimplifying. People who come to immunology with a broad base in other disciplines are likely to do better. Immunology became attractive because there were a lot off new molecules to discover and you could study cells in dishes and write lots of papers. The problem is that in order to understand it you need to have a common sense grasp of complex dynamic systems. Not that many people have that. So we get ideas like 'cytokine balance' or 'TH1-TH2 balance' that are entirely bogus because balance is an inappropriate metaphor there. You might as well talk about oil-petrol balance in a car. Oil and petrol have quite different jobs.
So it might seem hopeless, but this is what happened in RA. I spent ten years studying tissue structure and physiology and in the process found I was looking at unique features of joint lining tissue that seemed to have immunological implications. I had not been much interested in the detailed immunology at that point, although clearly we knew it was an autoimmune disease. So I spent five years learning the detailed immunology. I was then able to construct a theoretical model with tight system dynamic structure with 55 steps that could explain everything about the disease. It might not be correct in every detail but it made a key prediction - that targeting B cells was much more likely to be helpful than targeting T cells. So I did that and it turned out to be correct. We now have an excellent anti-B cell treatment and everyone has forgotten trying to target T cells.
Meanwhile, it gradually became clear to me that none of the immunologists actually understood my model. Their simple metaphors for cytokine balances etc left them unable to understand why it would work. So even today there are probably no more than a dozen people in the world who understand why rituximab was developed for RA, or why RA is a perfectly explainable disease. They carry on putting in grant applications for work that does not need to be done. The same people sit on grant committees so we have people studying irrelevances such as regulatory B cells or the microbiome.
But that in one sense does not matter because the patients are well on their rituximab. The pity is that rituximab is not the perfect solution and it would be good to do better and I see no evidence of any further progress because nobody understands what needs to be done. There is one exception, however, and that is Dr Andreas Radbruch in Germany. And all that is needed is for one person to understand and make the next step. It is hard for people to make headway in a community of colleagues who hold the purse strings and have no idea but science was always hard.
So the question is....how do we get Hr. Radbruch interested in ME.
Keep these questions in mind, we may well have a chance to seek clarification in the near future.
Could you be persuaded to drop them a line? I would be very surprised if Dr Montoya would not welcome your input.
My feeling is that part of the problem may be that there is now so much that one needs to know and understand in order to make progress in some fields, that fewer and fewer people are capable of so doing. Moreover, there seem to be more and more people with insufficient knowledge and understanding who are making judgements about funding and publications, resulting in more and more bad research, which is then cited by others, and so on.
I wonder to what extent this may be an inevitable consequence of the rapid progress that was made in the 40 years period you referred to, and whether we may be approaching a limit.
It is hard to email someone and say you think they are oversimplifying!
I don't think we are approaching a limit. As knowledge increases concepts can often actually be simplified and made easier to learn because they are explainable. I just think that the whole community have got sloppy and obsessed with money. It is perfectly possible to learn what is needed. But it requires searching the older literature carefully. And it requires a sense that one might not know everything!
I have no experience, but I had assumed that most scientists would welcome the opportunity to discuss their work with someone who has relevant and rare experience/knowledge – particularly from someone with no competing interests. But I accept your judgement if you feel it would inappropriate. Perhaps you will get an opportunity discuss ideas with him if you are both at IiMER colloquium next year.
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