I have chatted here before but now I can say that I’ve just joined the doin-rapa set, but through a different door than most. I’m a 66yo 5-yr post liver transplant who’s come back from metabolic catastrophy, and am now in vigorous good shape and health (save for some residual stage 3 chronic kidney disease, leftover from fatty liver cirrhosis hepatorenal syndrome).
As soon as I started feeling good after transplant, I began to advocate for less and less Immune-Suppressing (IS) medicine (Tacrolimus and Mycophenolate). I eventually got down to .5g Tac (1X), and 250mg MF (2X/day), a year ago. Yet, through all the dose reductions, I’ve never had any organ rejection activity, and have maintained nicely low liver enzymes.
So, when I talked to a transplant doc at my checkup Friday, before making my pitch, I brought up two human-trial research reports by Josh Levitsky MD, et al (Northwestern U, Chicago).
One was about converting liver transplant patients’ immunosuppression from Tacrolimus (a Calcineurin Inhibitor) to Sirolimus (mTOR-I), primarily to escape tacrolimus nephrotoxicity. They successfully converted most of the people, and collected data on biomarkers and the distribution of immune cell phenotypes, which might indicate changing immune suppression status.
The other trial was about weaning liver transplant patients off of Sirolimus, to achieve “Transplant Tolerance”.
This is fascinating. Tolerance is that state where the adaptive immune system functions normally, with respect to finding and fighting infections and cancer, yet accepts a transplanted organ as self, with no IS.
And somehow, using Rapamycin IS facilitates changing the mix of T and B and Dendritic cells that regulate the behavior of the immune response, towards Transplant’s Holy Grail: IS-free Tolerance.
And that kind of rhymes with the 2014 Joan Mannick MD Novartis study of increased vaccine response (titers), and decreased sickness in old people after several weekly 5mg everolimus doses.
Anyway, my doc was indeed familiar with these trials and, he accepted my pitch to let me go for it. So I am now off the old drugs and on 2mg/day Sirolimus (as “Rapamune”), with intent to wean the dose over time. I am very happy about this.
Of course, I’d rather do bigger doses less often. Full time mTOR suppression is a drag, plus I think the rapa-induced immune cell modifications last longer than the time between doses, even if it were just once a week.
Nevertheless, I’ll follow the Dr.'s daily-IS protocol. But sometimes a couple pills, you know, kinda roll to the back of the shelf for a while, only be found and taken all together later).
And that’s my story, so far.