Rapamycin, via the ol' Transplant angle

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.


Please keep us updated as you progress. Rapamycin’s effect on the immune system may be more important than any anti-aging effect. Rapa seems to make the immune system more effective against cancer, and my help with auto immune illnesses like Chrons disease.


Right, I have, or had autoimmune thrombocytopenia, causing low platelets. So I was put on heavy Prednisone, sometimes 100mg/day for months. This is your hyperinsulinemia / hyperglycemia metabolic-syndrome --on steroids. It drove fatty liver towards cirrhosis. And so Mycophenolate, which I took for IS, is sometimes prescribed for ITP. Now, Sirolimus is my only IS, and we’ll see how the autoimmunity vs mTOR suppression plays out.

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Your experience is fascinating. I am also a transplant patient (kidney, 13 years ago) and went through similar steps long ago by stopping Tacrolimus and taking a reduced dose of Rapamycin - only 1 mg per day. My goal was to wean myself off of Rapamycin by gradually reducing the dose to develop tolerance. I started taking it every other day at first, then 3 times per week. I have been on 1 mg/day for 4 days with 12 day break between doses for years now. It did not affect my transplanted kidney at all, all my bloodwork markers are very good. I do not want to completely stop Rapamycin and plan to continue the current protocol which I believe has anti-aging properties.


Dang, my husband had a kidney transplant in 1967( experimental at UW Madison) he passed in 2011 from Merkel cancer . So wish we had had knowledge of RApamyacin years ago. I have a feeling it would have been life changing.


It turns out liver transplants have the least immunosuppressive requirements of all organ transplants. AND, if you receive a liver and anything else from the same person, the liver’s immune quiescence is conferred to the other things, too.
The liver, it turns out, faces an onslaught of incoming irritants, foreign proteins and antigens, because the outgoing blood from all the digestive tract goes through the liver before entering general circulation. It has a sophisticated supply of lymphocytic stem cells, a few of which may work together with the recipient’s immune system, establishing a micro chimerism. That enhanced protection shields the other same-DNA organs, too.


Yet but he survived what, 44 years, and starting back in the in the Predni-Stone-Age, gadzooks!

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His story is pretty amazing. His original anti rejection was very heavy dosing of prednisone and Imuran. They gradually decreased his dose through the years to about 1/3 of original.