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Loss of TRPM3 ion channel function in natural killer cells from CFS/ME patients


Senior Member
Reading this groups last paper (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217865/) I recall being one of the most difficult paper's to follow and understand. I just tried to refresh my memory of it, and quite honestly I still don't follow parts of the experiments. Particularly why PregS requires thapsigargin as well to increase or restore effector function in NK cells. If they are saying in order to reverse the effects, they ALSO need to inhibit the function of an ion channeel/pump in the ER which has nothing to do with TRPM3, then why is that? Is the suggestion that PregS by itself is not enough stimulation to increase the intracellular gradient enough to restore effector function? I don't know, I might have expected the PregS alone to provide more restoration of effector function.

Anyway, I consider myself to be reasonably well equipped to read most papers, but I honestly cannot understand the nuts and bolts of this properly. It's difficult to be excited by paper's that I don't understand well.

Previous papers identified:
  • NK effector Function is known to be reduced in ME/CFS
  • TRPM3 Single Nucleotide deficiencies (SNP's) in TRPM3 genes have previously been identified in ME/CFS patients as a possible common genetic mutation
This group demonstrated:
  • Intracellular stores of Calcium Ions in ME/CFS patient NK cells are abnormal, leading to reduced effector function in NK cells
  • Stimulating ME/CFS patients NK cells with thapsigargin & PregS restores NK effector function
Very interesting, thank you for sharing. I would like to give a try with Thapsigargin, but cannot find where to find it...seems it is not yet sold as a medical drug...

M Paine

Senior Member
Auckland, New Zealand
I wouldn't suggest trying Thapsigargin as a treatment... I mean, it doesn't even work by itself in the paper (PregS was required as a co-treatment in their experiments). That's not even taking into account all the other risks and problems with that treatment strategy.

I don't mean to take a dig at you, but just in general as patients, if we are too quick to try risky/untried treatments outside of the supervision of some sort of clinical trial (or a drug that's already passed safety/efficacy trials for another disease), we run the risk of alienating the research community. We already have leading researchers who will not share their findings due to the risks of patients self treating, and for good reason. But more importantly, it could make your health worse :(