Preprint Spironolactone for ME/CFS in a Patient Homozygous for rs5522 (I180V): A Case Report, 2026, Donnellan et al

DonnellanP said:
I want everyone to feel better.

Honestly, I’m gotten some online harassment since the pre print so if I seem short, I’ve just been through some “ people “ getting really pissy about what I put out in the world. I read every reference throughly.
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Sorry to hear you've been experiencing that. We all want people with ME/CFS to get effective treatments too. On this forum we go through papers in-depth, which is why we are interested in the details. We'd be very interested to know the raw data and your process for determining that you had the Ile180Val mutation
 
jnmaciuch said:
I linked it earlier in the thread, it looks like the original version did not include this thread's author (and did not include reference to ME/CFS)
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The only reference to ME/CFS is in relation to the case report from this thread.

There is a claim about how «hyperactivity mediated by brain rs5522» «contributes to ME/CFS», but no evidence is provided in the paper.
Aldosterone [32, 33] and cortisol [33, 38] are transcriptional activators of MR rs5522. However, EC50s and fold-activation by aldosterone, corticosterone and 11-deoxycorticosterone for the rs5522 haplotype have not been reported, which is our goal. Activation of rs5522 by a corticosteroid other than cortisol could provide clues to the unique physiological actions mediated by rs5522 in the brain MR.
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Nor has the binding of spironolactone and progesterone, two MR antagonists [39, 40] to rs5522 been investigated. Inhibition of brain rs5522 would provide a selective method for treating hyperactivity mediated by brain rs5522, which contributes to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
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I’m not sure who prevailed in the genetic discussion or whether it was resolved.

Regardless of mechanism, a well documented n=1 case history of symptom improvement is always welcome.

If the there is an improvement in the more common genotype that means that it is possible spiro might work for more patients.
 
Jaybee00 said:
I’m not sure who prevailed in the genetic discussion or whether it was resolved.

Regardless of mechanism, a well documented n=1 case history of symptom improvement is always welcome.

If the there is an improvement in the more common genotype that means that it is possible spiro might work for more patients.
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As I have taken spironolactone in the past, I will try to get a new prescription and try it, if I succeed to get it
 
Jaybee00 said:
And it helped you in the past? With which symptoms and about how much improvement?
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I have taken it many years for a completely different reason (PCO Syndrome) so I cannot say it. But I was already in the early years of ME / POTS, but undiagnosed, probably mild at that time as I was still able to work
 
Jaybee00 said:
I’m not sure who prevailed in the genetic discussion or whether it was resolved.
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Sorry, didn’t see this till now. Probably good to make note in the public thread, in case the preprint leads others to start seeking the drug or paying for genetic testing.

The author mentioned TT genotype twice now, so seems likely it is TT and not the genotype causing the mutation mentioned in the case study. AI seems to give the wrong information about that gene, probably getting mixed up by the reference genome—might explain the confusion in this case study if the analysis was done by AI instead of someone with genetics training. Unless the raw data for the gene can be produced and more than one month of improvement can be shown, maybe best to take with a hefty grain of salt?

Spironolactone is prescribed for a lot of things—acne, treatment resistant blood pressure, hormone replacement therapy, etc. If it was a magic bullet, seems unlikely that we wouldn’t have heard before.
 
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