Where do you see the results from this study? Please provide a link.
1mg/day for 8 days seems like an extremely low dose (or at least a short period and very moderate dose). Perhaps its the “bolus” type dosing (10mg to 20mg at once) that gets it past the blood brain barrier.
All the rapamycin researchers I’ve spoken to say they see penetration of the BBB even in pretty low doses in model organisms (mice, marmosets, etc.)… so this result you suggest is surprising.
It was 1mg/day for 8 weeks, not 8 days. The link is right under the table in my post above (here again).
Maybe a bolus dose does get into the brain but we don’t know without data. Do you have any relevant publications which show BBB penetration in model organisms at low doses?
There is no publication listed on the clinical trial record but the results are not default data (all other results related to cognition, adverse events etc are complete). The results themselves don’t look particularly compelling (perhaps why it isn’t published).
Sorry - yes, 8 weeks. But still, 1 mg/day is a pretty low dose.
I see and reviewed the link to the clinical trials.gov info - but while I may have missed it, those entries typically don’t publish the results of the studies, and I don’t see a link to any papers published based on the study. Did I miss that?
No papers published that I see but look through the results section – everything is filled out e.g.:
Yes - I find this really surprising. I’ve actually never seen results data published on the ClinicalTrial.gov website and didn’t (and still don’t really know) that they publish the actual results there. I thought all the results from these clinical studies was only published in follow-on papers (if at all).
I have no confidence that the results reported there are what @alexvpickering is interpreting them as. So - I’ve emailed Mitzi the PHD contact at the study to see if it is correct.
You should email them this study as well that showed that: “sirolimus at dosages 2–6 mg/day was unable to inhibit the brain mTOR pathway in patients with MSA” Rapamycin and the Issue of Getting Through the Blood Brain Barrier - #45 by adssx
So either it’s a problem of patients with MSA, or, even in healthy people, no matter whether sirolimus crosses the BBB, it does not inhibit brain mTOR.
i asked AI “does the rapalog everolimus crosses BBB?”
Yes, everolimus crosses the blood-brain barrier (BBB). Animal studies have shown that everolimus can penetrate the BBB in mouse and rat models, as well as in R6/2 HD transgenic mice, with higher concentrations in the brain compared to the plasma. This suggests that everolimus is able to enter the brain
1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980725/
2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599962/
3 https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-5-26/figures/1
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For some reason all my posts were flagged by the community as spam?
If you search for treatment: Rapamycin and filter by completed studies there are 407 studies with results posted and 580 studies without result. I would post link but it won’t let me now.
I have liked the posts and pinging @RapAdmin if he can unflag your posts.
Welcome to the forum by the way.
Its just because you’re a new user… so you are limited in some posting abilities. I’ll bump you up a level.
references from @pollux led to this in rats:
Here is another in mice (seems like high dose – 10 or 30 umol/kg aka 9 or 27 mg/kg but check my math). Also note that 100 pmoles/g is ~ 91 ng/g but again check my math.
Everolimus penetrates the blood-brain barrier in R6/2 HD transgenic mice . Plasma (A ) and brain (B ) everolimus concentrations were measured 4 and 24 hours after the last dose following two weeks of treatment (black-bar = 10 μmol/kg, cross-hatched bar = 30 μmol/kg).
Is anyone here taking everolimus? Just curious.
We have people using it, not sure how active they are in the forums right now: Everolimus instead of Sirolimus / Rapamycin? Anyone else trying?
An earlier post re the relative effectiveness of sirolimus vs everolimus crossing the BBB in mice.
incidentally some of the catalytic inhibitors cross the BBB quite nicely but are not yet approved drugs in humans.
