Hoosierfans
Senior Member
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Hey all — long time PR member and ME / CFS sufferer here.
I’m starting this thread to document my experience with Rapamycin / Sirolimus. Yes, I have ME / CFS (and Rapa has been discussed and tested here before), however I have some comorbid conditions that make me a *bit* unique.
I have post viral onset (mono 2006), which relapsed and remitted until I had my second child in late 2010. Since then, my health has been on the decline to the point that where I am severe (mostly bed and housebound). The unique symptom experience I have, which I’ve not seen mentioned here much, is an intense sunburn like pain all over my arms, legs and face. It also feels like it’s in my brain, and it’s 24/7. I have POTS as well, although it’s more on the side of pure OI / hypotension.
There’s a lot more to my story — what I’ve tried, what hasn’t worked (and why) but for now, I wanted to document what led me to Rapamycin in case others have similar test results / patterns:
— Severe anxiety / fight or flight mode and suicidal depression. These, along with the pain, led me to ketamine treatment. Which led me to research showing that Rapamycin extends the anti- depressant effect of ketamine.
https://www.nature.com/articles/s41386-020-0644-9
— while researching CRPS and central sensitization (likely the driver of my pain), I came across a recent case report of a woman whose CRPS and fatigue was DRASTICALLY improved when her docs added Rapamycin:
https://www.cureus.com/articles/166...eatment-for-complex-regional-pain-syndrome#!/
— Indeed, overactive mTOR is crucial in the maintenance of chronic pain: https://www.hindawi.com/journals/bmri/2015/394257/
—. For reasons discussed below, researchers are looking at overactive mTOR being a driver in ME / CFS:
Through PR posts and a lot of Dr Google, here’s what I could find on mTOR and why it may apply in my particular case (lab results / symptoms).
GENERAL: Rapamycin is an mTOR inhibitor that is most often used in transplant cases. However, its being studied in all sorts of chronic diseases and neurodegenerative diseases at doses much lower than used in transplant cases. Like all things immune related, amplifiying mTOR all the time or decreasing mTOR all the time isn’t desirable.
When mTOR is active, it generally inhibits autophagy. By blocking mTOR, rapamycin encourages autophagy and thus “clears out” “dirty” mitochondria. This is the main hypothesis for using it in ME / CFS. Dysregulation of mTOR also messes with metabolism (diabetes) and may lead to misfiled and aggregated proteins in neuro disorders. As a result, rapamycin is being studied in Alzheimer’s, Parkinson’s etc. Rapamycin inhibits TNF-A, IL-!b and IL-6. It also reduces microglial expression and in so doing reduces neuroinflammation and neuro excitation. Interestingly, it also increases cerebral blood flow (yay), and restores the blood brain barrier (double yay) by normalizing and improving cerebral vasculature. (I have a host of neurological symptoms).
PAIN: In pain conditions, there is evidence that overactivated mTOR is responsible for maintaining chronic pain states. There are a few studies of using rapamycin in pain conditions (mostly rat studies of RA, Lupus, MS) where it was found useful. In one study of Rheumatoid arthritis, human patients took .5 mg every 2 days for 6 months. 50% of patients reduces or eliminated their disease. It’s also been used successfully in Lupus.
ME / CFS: The antectodal evidence in the ME / CFS community is that it tends to be helpful for those folks that have some sort of autoimmune process going on. Although rheumatologists have dismissed them, I have positive Cunningham antibodies and Cell Trend antibodies — importantly on those tests I have high levels of AT1R and ETAR antibodies, which cause microvascular endothelial cells to lose their wound healing ability. I found one study where Rapamycin restored this wound healing ability in folks with those antibodies. It seems to help with brain fog, energy levels and stability of CNS symptoms in those for whom it works.
The work of the folks at Simmaron Research is on ATG13, which is upregulated in ME / CFS patients serum. Upregulated ATG13 leads to overactive microglial cells, excessive reactive oxygen species (ROS) which damage mitochondria, and excess iNOS and Nitric Oxide, which leads to problems with hypotension, orthostatic intolerance and POTS. And, importantly, it also blocks autophagy.
TESTING: From what I’ve read, there’s no commercially available test to tell us whether mTOR is overactive and thereby I would benefit from rapamycin. In my particular case, I took at look at any abnormal lab markers I’ve had to see if they have any connection to mTOR. Of note, I have extremely high levels of leucine (the amino acid). Leucine is a major trigger for mTOR to be overactive. In addition, high VEG-F levels (I’m consistently high) can also be caused by high mTOR (vascular proliferation). Lastly, CCL5 (RANTES) is high on my cytokine panel, in addition to TNF-a, IL-6 and IL-1B. Lastly, I have certain antibodies (noted above) that may be involved in triggering mTOR.
mTOR is known to be hijacked by viruses, in order to let viruses proliferate and survive. So viral testing might be helpful to determine if someone might benefit from Rapamycin. I haven’t had viral testing done lately, but will be doing a panel shortly and monitoring titers as my Rapamycin experiment progresses.
DOSING: Consistent with experience here, I’ll be trialing 1 mg 2 x week and moving up 1 mg each of those days each week, to a maximum of 3 mg 2 x week. I’m fortunate in that I have a PCP who will let me experiment with dose timing to see what might work best.
We may also trial a dose of 6 mg prior to a ketamine infusion to see what effect that may have.
Hope this provides some with additional info regarding mTOR. There are folks on this forum with vastly more scientific knowledge than I, but hopefully this provides some basic information and framework that is “brain fog” friendly. All of this information was what I provided to my PCP in order to foster the discussion of a Rapamycin trial.
I’m starting this thread to document my experience with Rapamycin / Sirolimus. Yes, I have ME / CFS (and Rapa has been discussed and tested here before), however I have some comorbid conditions that make me a *bit* unique.
I have post viral onset (mono 2006), which relapsed and remitted until I had my second child in late 2010. Since then, my health has been on the decline to the point that where I am severe (mostly bed and housebound). The unique symptom experience I have, which I’ve not seen mentioned here much, is an intense sunburn like pain all over my arms, legs and face. It also feels like it’s in my brain, and it’s 24/7. I have POTS as well, although it’s more on the side of pure OI / hypotension.
There’s a lot more to my story — what I’ve tried, what hasn’t worked (and why) but for now, I wanted to document what led me to Rapamycin in case others have similar test results / patterns:
— Severe anxiety / fight or flight mode and suicidal depression. These, along with the pain, led me to ketamine treatment. Which led me to research showing that Rapamycin extends the anti- depressant effect of ketamine.
https://www.nature.com/articles/s41386-020-0644-9
— while researching CRPS and central sensitization (likely the driver of my pain), I came across a recent case report of a woman whose CRPS and fatigue was DRASTICALLY improved when her docs added Rapamycin:
https://www.cureus.com/articles/166...eatment-for-complex-regional-pain-syndrome#!/
— Indeed, overactive mTOR is crucial in the maintenance of chronic pain: https://www.hindawi.com/journals/bmri/2015/394257/
—. For reasons discussed below, researchers are looking at overactive mTOR being a driver in ME / CFS:
Through PR posts and a lot of Dr Google, here’s what I could find on mTOR and why it may apply in my particular case (lab results / symptoms).
GENERAL: Rapamycin is an mTOR inhibitor that is most often used in transplant cases. However, its being studied in all sorts of chronic diseases and neurodegenerative diseases at doses much lower than used in transplant cases. Like all things immune related, amplifiying mTOR all the time or decreasing mTOR all the time isn’t desirable.
When mTOR is active, it generally inhibits autophagy. By blocking mTOR, rapamycin encourages autophagy and thus “clears out” “dirty” mitochondria. This is the main hypothesis for using it in ME / CFS. Dysregulation of mTOR also messes with metabolism (diabetes) and may lead to misfiled and aggregated proteins in neuro disorders. As a result, rapamycin is being studied in Alzheimer’s, Parkinson’s etc. Rapamycin inhibits TNF-A, IL-!b and IL-6. It also reduces microglial expression and in so doing reduces neuroinflammation and neuro excitation. Interestingly, it also increases cerebral blood flow (yay), and restores the blood brain barrier (double yay) by normalizing and improving cerebral vasculature. (I have a host of neurological symptoms).
PAIN: In pain conditions, there is evidence that overactivated mTOR is responsible for maintaining chronic pain states. There are a few studies of using rapamycin in pain conditions (mostly rat studies of RA, Lupus, MS) where it was found useful. In one study of Rheumatoid arthritis, human patients took .5 mg every 2 days for 6 months. 50% of patients reduces or eliminated their disease. It’s also been used successfully in Lupus.
ME / CFS: The antectodal evidence in the ME / CFS community is that it tends to be helpful for those folks that have some sort of autoimmune process going on. Although rheumatologists have dismissed them, I have positive Cunningham antibodies and Cell Trend antibodies — importantly on those tests I have high levels of AT1R and ETAR antibodies, which cause microvascular endothelial cells to lose their wound healing ability. I found one study where Rapamycin restored this wound healing ability in folks with those antibodies. It seems to help with brain fog, energy levels and stability of CNS symptoms in those for whom it works.
The work of the folks at Simmaron Research is on ATG13, which is upregulated in ME / CFS patients serum. Upregulated ATG13 leads to overactive microglial cells, excessive reactive oxygen species (ROS) which damage mitochondria, and excess iNOS and Nitric Oxide, which leads to problems with hypotension, orthostatic intolerance and POTS. And, importantly, it also blocks autophagy.
TESTING: From what I’ve read, there’s no commercially available test to tell us whether mTOR is overactive and thereby I would benefit from rapamycin. In my particular case, I took at look at any abnormal lab markers I’ve had to see if they have any connection to mTOR. Of note, I have extremely high levels of leucine (the amino acid). Leucine is a major trigger for mTOR to be overactive. In addition, high VEG-F levels (I’m consistently high) can also be caused by high mTOR (vascular proliferation). Lastly, CCL5 (RANTES) is high on my cytokine panel, in addition to TNF-a, IL-6 and IL-1B. Lastly, I have certain antibodies (noted above) that may be involved in triggering mTOR.
mTOR is known to be hijacked by viruses, in order to let viruses proliferate and survive. So viral testing might be helpful to determine if someone might benefit from Rapamycin. I haven’t had viral testing done lately, but will be doing a panel shortly and monitoring titers as my Rapamycin experiment progresses.
DOSING: Consistent with experience here, I’ll be trialing 1 mg 2 x week and moving up 1 mg each of those days each week, to a maximum of 3 mg 2 x week. I’m fortunate in that I have a PCP who will let me experiment with dose timing to see what might work best.
We may also trial a dose of 6 mg prior to a ketamine infusion to see what effect that may have.
Hope this provides some with additional info regarding mTOR. There are folks on this forum with vastly more scientific knowledge than I, but hopefully this provides some basic information and framework that is “brain fog” friendly. All of this information was what I provided to my PCP in order to foster the discussion of a Rapamycin trial.
