Impaired oxygen sensitivity of red blood cells from ME/CFS, Wan NIH talk 2024

[Jaybee00]

Talk around the 2:29 mark.



Worth watching—has identified 2 compounds that can improve the deformability of red blood cells of MECFS patients in vitro.

H/T Murph from PR.

 

[SNT Gatchaman]

Link at time-stamp https:// youtu.be/Uei0XjFxXSM?t=2h28m30s

 

[Ravn]

Copying my post from the NIH news thread as it's more relevant here

Has anyone watched Jiandi Wan's section (starts 2:28)?

I watched a bit mainly because the name was unfamiliar which made me curious. Turns out he presents quite a bit of unpublished data but I struggled to follow it though I gather red blood cell deformability is still or again on the agenda

According to Wikipedia the drugs mentioned in the slide below are a long-acting β 2 adrenergic receptor agonist used in asthma and COPD (Salmeterol) and a small molecule muscarinic acetylcholine receptor agonist (Xanomeline). I didn't catch why they were chosen

And I'm guessing(!) PO2 stands for partial pressure of oxygen, i.e. how much oxygen gas is dissolved in the blood

 

[Jaybee00]

Salmeterol is a bronchodilator available as an inhaler as well as in tablet form.

Xanomeline is being developed as a schizophrenia drug.

https://en.m.wikipedia.org/wiki/Xanomeline

 

[SNT Gatchaman]

Two of the published papers discussed in this talk are —

Oxygen tension–mediated erythrocyte membrane interactions regulate cerebral capillary hyperemia (2019, Science Advances)

Erythrocytes Are Oxygen-Sensing Regulators of the Cerebral Microcirculation (2016, Neuron)

 

[Simon M]

Some notes on Jiandi Wan's very interesting presentation

• Great to have an existing expert in a technical field start working on MEcfs. I think we need much more of this.
• It makes sense that RBCs are sensitive to local oxygen concentration becoming more flexible and so moving faster through capillaries, increasing O2 delivery to restore local oxygen levels.
• The reduced responsiveness to pO2 they found in MEcfs also makes sense and could explain the reduced cerebral blood flow, as well as lower responsiveness to falling O2 levels in the rest of the body.
• Plus they have a tool for testing pO2 responsiveness. And this functional test detects differences not seen in standard lab tests (e.g. volume, shape).
  
• The testing of the effect of various drugs on RBC oxygen responsiveness is also pretty neat.

Some concerns:

• I'm not sure we can conclude much from the changes from baselines seen in individual patients. As Vicky W pointed out, there were complex changes to a drug cocktail, and no evidence the RBC changes seen reflected changes in symptoms of function.
• The 'diagnostic' accuracy is poor at 80% given the accuracy was presumably tuned to this dataset. As usual: 1. does this replicate using the same cutoffs in a new study? 2. Can this differentiate not from HCs but from sick controls? It seems premature to push ahead with a diagnostic test before this has been established.

But I'm looking forward to seeing what they do next.