2023 IIMEC15 - Alain Moreau

YouTube: IIMEC15 07 Professor Alain Moreau 15th Invest in ME Research International ME Conference 2023

Discussion of potential biomarkers in ME/LC subgroups. References upcoming, unpublished work. Highlighted time-stamps —

9:07 MicroRNAs
18:18 SMPDL3B
27:03 FGF-21

SMPDL3B is Sphingomyelin Phosphodiesterase, Acid-Like 3B.

I'm not sure how much we have on SMPDL3B but we have tags for papers on sphingomyelin and FGF21.

 

The bit about generally lower, and for some asymmetrical between left and right hemispheres, cerebral oxygen levels was quite interesting (though brief). There is a little more in the Q&A at the end as well.

More evidence for a problem with oxygen delivery in some form, is what I take from that.

 

PEM clearly has two stages, the one during and right after exertion and the crash that happens a day after. Any study with PEM should investigate both.

 

That's what I meant, when patients exert themselves in a way that leads to a crash days after, they need to measure not just the crash but also what happens in the previous day(s). We need to have all the data without underlying assumptions.

 

In their research, Workwell has documented that some symptoms of PEM show up fairly soon after the onset of exercise (link) and have suggested that if patients are able to recognize these early symptoms, they can reduce the severity and/or duration of PEM by stopping/reducing the trigger.

Admittedly anecdotal but that seems to fits what I've seen with one patient - head pressure within 20-30 minutes of browsing on a phone while supine, headache if they went longer and if they went longer still, a next day crash rolled up in a ball with whole body pain. But that next day full crash didn't happen if they kept the browsing short.

Is this part of what other patients do when pacing? And what would that early onset of worsened symptoms be called if not PEM. Wouldn't it be important to study PEM across its time course from triggering event to "resolution"?

I have mixed feelings on this approach...
Studies using exercise challenges have provided significant evidence of the ME abnormal response to exertion but are hard on the person with ME. If as above, PEM can have differing levels of severity and duration depending on the magnitude of the trigger, is this a gentler way of invoking the disease enough to see those changes?
But I'd like to see how it compares to CPET study findings. I don't think that's been done yet and there are also few if any studies outside of one lab.

 

Do we know if immediate PEM is the same or similar as delayed PEM?

 

Good points. AFAIK, the studies of PEM have not looked at the cumulative effect of multiple triggers. Leaves me wondering how such a study would be conducted/what would be required.

 

If I have a moment of respite I can actually feel it coming. It's more about awareness with me, take a moment to actually feel yourself out. The problem is that when I'm tired I lose track of basically everything because of brain fog and I start doing stupid stuff. I'm on the computer for way too long now for example after an intense 1,5 hours of walking around with my nephew catching pokemon this afternoon . If you hadn't collective brought this up I probably would've gone on, but now I'm gonna turn in for the night after some relaxing telly.

 

I agree its not sufficient to just monitor the post-trigger response for 90 minutes.

But would that imply there are two separate biological processes going on, one for the immediate response and one for the next day response?

Or could the evidence suggest there's one process/cascade of processes where the severity and duration depends on the person's baseline, the nature and magnitude of the trigger or triggers, genetics, etc

 

Agree with this.

 

I agree that Dr. Moreau plays a little too fast and loose with the term PEM in regards to his massage cuff, but I'd also say that for most of his results, the before and after aren't really important at all (mostly it's the difference between the controls and the patients overall, not specifically in their response to the stressor).

But also, I think the difference in the cognitive testing results before and after the stressor, whatever you want to call it, are pretty compelling that something is going on. Reduced cognitive capacity as a fairly immediate effect also accords with my own experience. Ideally, they'd also do tests the next day or two days later, but if this is an abnormality that they can run with that's more practical to test, then that seems like a pretty good thing.

 

See —
The Lipid-Modifying Enzyme SMPDL3B Negatively Regulates Innate Immunity (2015)
A novel estrogen receptor 1: sphingomyelin phosphodiesterase acid-like 3B pathway mediates rituximab response in myositis patients (2022)