I really think this idea that MECFS pathology is totally brain based is not the occams razor type approach people seem to think it is
Thanks, would be good to have more discussion about this and an overview of arguments pro and contra. I've tried to reply to your points below.
you have to ignore one of the most significant gene hits in DecodeME in BTN2A1 (now somewhat replicated) and the possible interferon connections of OMLF4, the immune activation symptoms many people get when they crash - runny noses, swollen lymph nodes etc.
BTN2A1 also featured prominently in GWAS on anxiety (see
here and
here) while OMFL4 was one of the pleiotropic genes
associated with multiple neuropsychiatric traits such as ADHD, schizophrenia, depression, and autism. So instead of ignoring these hits, the idea is that they show up because of a brain-related rather than immune function. This would fit much better with all the other signals in DecodeME.
You have to ignore the Ryback, Mensah, Cliff, Missalidis studies, the Cambridge uni teams IFNy finding in Long Covid, be absolutely certain daratumumab does nothing (it may do but its far to soon to dismiss it), conpletely dismiss the cyclo studies, etc etc.
This has been discussed in depth elsewhere but most of these studies actually found no (clear) sign of immune involvement. I've recently summarised the evidence on the immune system in ME/CFS in this article and there was very little to go on.
In this article, we have made a comprehensive overview of research findings on the immuneContinue readingThe immune system in ME/CFS
mecfsscience.org
Daratumumap and cyclophosphamide were open label studies and the Rituximab saga showed has misleading these can be. Unfortunately, there's almost no scientific justification of why these treatment would work in ME/CFS other than anecdotal reports.
So, there isn't anything to ignore or dismiss. Other than ME/CFS often having an infectious trigger there's almost no convincing evidence of immune involvement. If there was a reliable immune lead we would be all over it and analyse its implications in detail. But there's very little to play with...
I'm not saying brain only is impossible. I'm just not sure it's the most logical conclusion from the evidence we have. But of course I have to acknowledge my bias to wanting a better understood pathology...
Think this is an important point because I feel like the entire ME/CFS field seems to have this bias.
Currently, almost nobody seems to be taking the neuronal pathology hypothesis seriously. Everyone is looking in another direction: viral persistence, autoantibodies, blood cloths, mitochondrial damage, endothelial dysfunction, muscle damage, cerebral blood flow, intracranial pressure, complement activation, trained immunity, craniocervical instability, metabolic traps. It almost looks like everything is being considered except what the genetic evidence points to!
Even the people doing brain scan studies and autopsies are talking about neuroinflammation when their own studies show the opposite. The DecodeME preprint also tried to highlight immune findings (gene mutations that weaken the immune response to infections) while the data do not point in this direction.
So I feel like there's a strong bias in the field where people expect an immune or metabolic pathology and try to fit their data into this perspective. It probably also plays a role that a focus on the brain has been associated with bogus psychosomatic theories. But the proper response would be to ignore this, not try to form a counter-response.
To clarify: I think multiple lines of research need to be explored and these genetic findings (or my interpretation of them) may certainly be flawed. But the balance now seems quite off. I think the genetic pointer to neurons is the most valuable ME/CFS lead we have at the moment.
