Preprint Biological Insights from Genome-Wide Association Studies and Whole Genome Sequencing of [ME/CFS], 2026, Maccallini et al

[neophyte32]

People do not improve or recover to the extent that people clearly do in e.g. Fluge and Mella's studies in degenerative diseases.

How would your own experience of getting better for 12 months track with the idea of irreversible neuron loss causing MECFS?

or perhaps it only concerns the most severe cases... the gap is so wide between mild and severe, there may indeed be a loss of neurons in a specific area.

 

[V.R.T.]

or perhaps it only concerns the most severe cases... the gap is so wide between mild and severe, there may indeed be a loss of neurons in a specific area.

But again, you've got people who improve from severe or very severe to moderate or mild, like the prominent German advocate Martin (pausedME is his username in various places i think) you've got people like me who improve back to the top end of severe from borderline very severe and highly sensitive to all stimuli. You have many case studies and reports of severe people who are much better after x or y drug. So even if those drugs don't work, those people really improved. If severe symptoms were caused by irreversible neuron loss that wouldn't happen.

I suppose until we know the mechinism enough for effective treatments to be developed there is always a possibility of the whole permanent untreatable thing, but I'm not sure I buy it.

 

[V.R.T.]

and @V.R.T. (if I'm remembering correctly), I *was* trying to jog my way out of it right up until I was properly disable

Actually i didnt do much exercise at all during my prodromal phase. I tried to jog my way back into health 3 and a half years into mild MECFS after being gaslit by doctors.

My sense is the prodrome phase involves a lot of feeling ill/awful, not responding normally to exercise, plus cognitive, brain fog and/or mood problems (not to mention various gut and other 'autonomic' things seemingly going a bit haywire).

This is about right though. No PEM to speak of (at least not that I could be certain of) but something wasn't right.

 

[neophyte32]

But again, you've got people who improve from severe or very severe to moderate or mild, like the prominent German advocate Martin (pausedME is his username in various places i think) you've got people like me who improve back to the top end of severe from borderline very severe and highly sensitive to all stimuli. You have many case studies and reports of severe people who are much better after x or y drug. So even if those drugs don't work, those people really improved. If severe symptoms were caused by irreversible neuron loss that wouldn't happen.

I suppose until we know the mechinism enough for effective treatments to be developed there is always a possibility of the whole permanent untreatable thing, but I'm not sure I buy it.

I've talked to Martin privately on Twitter a lot, and I know about his treatment. Huge doses of pregabalin every other day, and very high daily doses of lorazepram. He added lamotrigine a few months ago. He's a very rare example of someone with very severe symptoms who has recovered (he fluctuates between mild and moderate now). The treatment is very, very heavy and dangerous in the long term, he knows it.

You're right, there's no proof of neuronal damage. Paolo doesn't know either, but he doesn't rule out the possibility.

LDA helped me go from 300 steps (I'm back to that unfortunately) to 1700 steps for 5 months without too much trouble, with no sensitivity to light, etc. The effect was too short-lived... I'm trying again after a two-month break, but well... it doesn't seem to be working again.

Yes, there's definitely something possible. We are still a long way from knowing, but perhaps with people like Paolo and Edwards we will eventually make progress.

 

[Andy]

He's a very rare example of someone with very severe symptoms who has recovered (he fluctuates between mild and moderate now).

So he hasn't recovered, as most people would understand it. A better word to use in my opinion is that he has improved.

 

[neophyte32]

So he hasn't recovered, as most people would understand it. A better word to use in my opinion is that he has improved.

Yes, you're right, I misspoke. He has made enormous progress, and VRT is right to point that out. He was bedridden, immobilized, and fed through a tube for years. But his treatment is extremely intensive.