• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas

Messages
38
So, no silver bullet here- we completed a 10 day trial of Rapamune and had no noticeable improvement.

We ordered 30 pills for about $190 on 5-2-17 from ( https://www.allgenericmedicine.com/product/rapamune-1mg/601 ) and received them in Colorado on 5-18-17. The hope was that they were as represented on the web site and were brand name Wyeth Rapamune- they weren't. We received a manilla envelope containing 5 blister packs of 6 pills marked as Sirolimus made by Emcure Pharmaceuticals. In an attempt to verify what we got I sacrificed one pill to test the only physical property I could without a lab, I ground up a pill and tested it's solubility in water and ethanol. As per the properties of Rapamune it was not soluble in water and was in ethanol, I guessed it was the real stuff.

We started with 1mg. per day for the first three days with no improvement, we then added a glass of grapefruit juice with the 1 pill for 3 days. As per this study ( https://news.uchicago.edu/article/2...ice-lets-patients-take-lower-dose-cancer-drug ) the grapefruit juice increases the absorption by a factor of about 3. We then increased to 2 pills per day plus the grapefruit juice for 4 days (an effective dose of 6mg. per day). At the end of the 10 days there was no reduction in any of my wife”s major or secondary symptoms so we stopped the Rapamune but on day 12 she woke up with mouth ulcers which took about 3 days to clear up. Mouth ulcers are the most common reported side effect of Rapamune so we're guessing it was in fact the real drug and she was absorbing it.

Once again, I am either treating or torturing her, I just don't know which until it's over.

On a positive note- we started anti-viral treatment with Arbidol immediately after stopping the Rapamune and her IRIS or herx reaction was almost zero for the first week of Arbidol, it has since come back but it was nice for her not to have any additional suffering with the anti-viral for awhile. I am uncertain about using the Rapamune with the Arbidol and I'm still investigating the possible interactions

For those considering using Rapamune there are some interesting discussions about the dangers relative to the dosage on these web sites-
https://rapamycintherapy.com/
https://joshmitteldorf.scienceblog.com/2016/06/13/rapamycin-redux/
http://www.longecity.org/forum/topi...ifespan-anyone-experimenting-with-this/page-1

The life extension people are very interested in Rapamune/Sirolimus/Rapamycin and there are several people using low dosage pulsing treatment in N=1 testings
 

XenForo

Senior Member
Messages
107
...we completed a 10 day trial of Rapamune and had no noticeable improvement...
That's a bummer. It's so frustrating trying to figure out what we'll respond positively to.

(Unrelated,) here are a couple papers that together indicate that rapamycin's risk of lymphoma is associated with infection with Epstein Barr virus and or HHV8:

Human Herpesvirus-8 (HHV-8)-Associated Primary Effusion Lymphoma in two Renal Transplant Recipients Receiving Rapamycin: https://moscow.sci-hub.cc/25eff1f76ff35371c8b45b720b8735da/boulanger2008.pdf

Rapamycin inhibits the interleukin 10 signal transduction pathway and the growth of Epstein Barr virus B-cell lymphomas: http://cancerres.aacrjournals.org/content/63/15/4472.long

It sounds like most people have been exposed to Epstein Barr Virus (EBV), and therefore latent EBV is in most of us.
 
Last edited:

dreampop

Senior Member
Messages
296
So, no silver bullet here- we completed a 10 day trial of Rapamune and had no noticeable improvement.

We ordered 30 pills for about $190 on 5-2-17 from ( https://www.allgenericmedicine.com/product/rapamune-1mg/601 ) and received them in Colorado on 5-18-17. The hope was that they were as represented on the web site and were brand name Wyeth Rapamune- they weren't. We received a manilla envelope containing 5 blister packs of 6 pills marked as Sirolimus made by Emcure Pharmaceuticals. In an attempt to verify what we got I sacrificed one pill to test the only physical property I could without a lab, I ground up a pill and tested it's solubility in water and ethanol. As per the properties of Rapamune it was not soluble in water and was in ethanol, I guessed it was the real stuff.

We started with 1mg. per day for the first three days with no improvement, we then added a glass of grapefruit juice with the 1 pill for 3 days. As per this study ( https://news.uchicago.edu/article/2...ice-lets-patients-take-lower-dose-cancer-drug ) the grapefruit juice increases the absorption by a factor of about 3. We then increased to 2 pills per day plus the grapefruit juice for 4 days (an effective dose of 6mg. per day). At the end of the 10 days there was no reduction in any of my wife”s major or secondary symptoms so we stopped the Rapamune but on day 12 she woke up with mouth ulcers which took about 3 days to clear up. Mouth ulcers are the most common reported side effect of Rapamune so we're guessing it was in fact the real drug and she was absorbing it.

Once again, I am either treating or torturing her, I just don't know which until it's over.

On a positive note- we started anti-viral treatment with Arbidol immediately after stopping the Rapamune and her IRIS or herx reaction was almost zero for the first week of Arbidol, it has since come back but it was nice for her not to have any additional suffering with the anti-viral for awhile. I am uncertain about using the Rapamune with the Arbidol and I'm still investigating the possible interactions

For those considering using Rapamune there are some interesting discussions about the dangers relative to the dosage on these web sites-
https://rapamycintherapy.com/
https://joshmitteldorf.scienceblog.com/2016/06/13/rapamycin-redux/
http://www.longecity.org/forum/topi...ifespan-anyone-experimenting-with-this/page-1

The life extension people are very interested in Rapamune/Sirolimus/Rapamycin and there are several people using low dosage pulsing treatment in N=1 testings

Sorry it didn't work. But I guess we're all pretty good at dealing with that at this point. I was surprised Grapefruit juice increased the Siroliumus' concentration because you said

"In our case we have a proven Coxsackie B4 infection in the wall of the small intestine which matches the absorption route of Rapamune so I'm more optimistic about it's potential effectiveness. It is involved in the CYP3A4 pathway so no grapefruit juice but otherwise it does not seem to interact poorly with other drugs" and my understand from wikipedia is "grapefruit can block the enterocyte CYP3A4 thereby affecting the medication absorption in the intestine.[7] If the medication is absorbed to a lesser extent, it may not reach a therapeutic level and its effect may be compromised.[7]"

So, I got confused somewhere along the way but I don't doubt the study (plus the ulcers). Good luck with Arbidol.
 

msf

Senior Member
Messages
3,650
Gosh, this article in Discover Magazine really helps me understand the basic immune issues here. It sees to focus on the work of Professor Jonathan Edwards: http://discovermagazine.com/2013/may/01-are-b-cells-to-blame-for-chronic-fatigue-syndrome
I had no idea Edwards helped inform Fluge and Mella. He seems to have his head wrapped around the immune issues more than anyone.

I would imagine that Prof. Edwards helped by developing the use of Rituximab in autoimmune diseases. Fluge and Mella decided to trial Rituximab after they gave it to ME patients with cancer and it ameliorated their ME symptoms. It might be that they were more confident in Rituximab´s potential in ME because of the Prof. Edward´s work in RA, but I am not aware of any direct co-operation between them.
 

XenForo

Senior Member
Messages
107
...we completed a 10 day trial of Rapamune and had no noticeable improvement.
I noticed continuing improvement for three or so weeks after stopping the rapamune. You'll have to see if you experience a similar improvement in the following weeks.
 

XenForo

Senior Member
Messages
107
I gave in and took another .5 mg Rapamune pill yesterday and today. It didn't help at all this time. This is so frustrating. I have pretty bad diarrhea, which rapamycin never really helped. And I have a headache that doesn't respond to rapamune either, now. I'll have to see if there's a delayed response. Argh. This is so different from the last time I took Rapamune; I wonder why it's so different this time.

EDIT: opps, the new medication I'm taking might be causing side effects of headache, fatigue and diarrhea.
 
Last edited:

XenForo

Senior Member
Messages
107
Hmmm. I feel like the Rapamune works when I take it along with morning ghee (clarified butter) and doesn't work when I don't. I'm not sure, and have no idea why that would make a difference. Although I thought I remembered reading that rapamycin effects cholesterol levels.
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
Hmmm. I feel like the Rapamune works when I take it along with morning ghee (clarified butter) and doesn't work when I don't. I'm not sure, and have no idea why that would make a difference. Although I thought I remembered reading that rapamycin effects cholesterol levels.

What benefits are you finding from it now?
 

XenForo

Senior Member
Messages
107
What benefits are you finding from it now?
"Brainfog" lifts, increased energy. Exercise intolerance greatly reduced. There's something else that's hard to describe, but I I feel something that I did when I was a little kid - really young. It's a vague feeling, but it feels great.

I should have mentioned that I'm on the ketogenic diet. No refined sugar, and actually not much really sweet food like apples either. Lots of fats and oils. It does seem to make a difference, as when I ran out of the main fat I use, the rapamune didn't seem to work at all. It was weird. Total brainfog and all day in bed and went "to bed" early. This syndrome is so confusing.
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
Someone I know taking 5mg Rapamune once a week for 5 weeks reports the following:
Oh man I don't even know where to start with the Rapamycin right now. But I'm at an activity level I haven't been at in a long time. For example last night I went out to dinner and drinks with some old friends. I got fatigued about an hour before we were done and it was all too familiar CFS total drained fatigue. However, I've barely been leaving the house except to buy groceries for the last few months
 

dreampop

Senior Member
Messages
296
Someone I know taking 5mg Rapamune once a week for 5 weeks reports the following:

Jesse, do you know if he has constant or relapsing/remitting CFS? Seems most responders are the later. 5mg is a huge dose, used for organ transplants - also carries a much higher risk of cancer.
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
This is really interesting, haven't seen it discussed yet. Rapamune has implications for autism as well (similar to Naviaux's work with Suramin)

It seems Rapamune may have effect on the brain, immune system, and metabolism (and possibly antiviral effects)

Article link
Study link

From the article...
Drs. Tang and Sulzer, and their team, also studied a particular mouse that is considered a research model for autism. This mouse has a mutation in the gene for tuberous sclerosis, which increases the risk for autism in people, and the mouse also has too many synapses. The researchers treated their mice with a drug (rapamycin) that decreased the number of synapses and improved social behaviors.

Rapamycin (also called sirolimus) is used in human patients with organ transplants to prevent rejection. Unfortunately, it can have severe side effects, including suppressing the immune system, lung inflammation, and risk for diabetes. Because of these side effects, it cannot be recommended for children with autism. But it is worth knowing that a very similar drug, called everolimus, is actually being studied in patients with tuberous sclerosis, a genetic disorder that causes tumors, cognitive impairments, and increases risk for autism.

And from the study...
Elevated mammalian target of rapamycin (mTOR) signaling has been found in Alzheimer's disease (AD) patients and is linked to diabetes and aging, two known risk factors for AD. However, whether hyperactive mTOR plays a role in the cognitive deficits associated with AD remains elusive. Here, we genetically reduced mTOR signaling in the brains of Tg2576 mice, a widely used animal model of AD. We found that suppression of mTOR signaling reduced amyloid-β deposits and rescued memory deficits. Mechanistically, the reduction in mTOR signaling led to an increase in autophagy induction and restored the hippocampal gene expression signature of the Tg2576 mice to wild-type levels. Our results implicate hyperactive mTOR signaling as a previous unidentified signaling pathway underlying gene-expression dysregulation and cognitive deficits in AD. Furthermore, hyperactive mTOR signaling may represent a molecular pathway by which aging contributes to the development of AD.
 
Last edited:

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
More on everolimus from Wikipedia. I've not seen everolimus discussed here either
In a similar fashion to other rapalogs, its effect is solely on the mTORC1 protein complex, and not on the mTORC2 complex. This can lead to a hyper-activation of the kinase AKT via inhibition on the mTORC1 negative feedback loop, while not inhibiting the mTORC2 positive feedback to AKT. This AKT elevation can lead to longer survival in some cell types. Everolimus has important effects on cell growth, cell proliferation and cell survival.

TSC1 and TSC2, the genes involved in tuberous sclerosis, act as tumor suppressor genes by regulating mTORC1 activity. Thus, either the loss or inactivation of one of these genes lead to the activation of mTORC1.[15]

Everolimus binds to its protein receptor FKBP12, which directly interacts with mTORC1, inhibiting its downstream signaling. As a consequence, mRNAs that code for proteins implicated in the cell cycle and in the glycolysis process are impaired or altered, and tumor growth is inhibited
 

XenForo

Senior Member
Messages
107
I needed to get some serious stuff done, and went back on Rapamune June 12th, so it's been 10 days now. I'm back to being productive again. I reviewed and revised some very confusing paperwork. And I did some serious demolition work, some of which involved a jackhammer. Man it feels great to feel "normal" again. I remember having this much energy when I was a little kid. However, the jackhammer was (of course) not really a good idea, as I've been a little too tired today to be as productive.
 
Last edited: