Human Rapamycin study - Prostate Cancer Prevention

Results of a human phase 1 study on rapamycin and prevention of prostate cancer have been recently published. There’s some interesting findings:

  1. They used an encapsulated version to resist gastric ph levels. The dosing regimens were very low at 0.5 mg and 1 mg per week , and a third group on 0.5 mg daily dosing. The encapsulated version improved bioavailability.
  2. There were more side effects in the daily dosing. More worrisome was a significant increase in naive T cell exhaustion in that group.
  3. Oddly, in the once a week dosing, blood levels returned to baseline after just 24 hours despite the long half life.
  4. Weekly doses once again just indications of improved immune function, similar to the Mannick study.

In summary, weekly dosing was associated with fewer side effects and a more favorable immune response.

2 Likes

I’m still trying to figure out exactly what eRapa is and whether it is functionally any different or better than the microcystal-based rapamune, or even the generics with their own proprietary encasulation/coating… sadly, I’ve not seen any 3rd party, head to head comparisons as of yet.

1 Like

Hmmm, I just tried to send an email to “Rapamycin Holdings” to learn more about their product… it bounced back as a dead email address. Seems like the company is not in operation.

In the past I had read that eRapa is what is typically used in animal clinical studies, but I’ve never heard of it being used in human clinical trials before (though haven’t looked into it much).

But, they seem to have a clinical study still going on:

Nanoparticle technology.

https://pdfaiw.uspto.gov/.aiw?Docid=20210386672&homeurl=http%3A%2F%2Fappft.uspto.gov%2Fnetacgi%2Fnph-Parser%3FSect1%3DPTO2%2526Sect2%3DHITOFF%2526p%3D1%2526u%3D%25252Fnetahtml%25252FPTO%25252Fsearch-bool.html%2526r%3D1%2526f%3DG%2526l%3D50%2526co1%3DAND%2526d%3DPG01%2526s1%3D%252522rapamycin%252Bholdings%252522%2526OS%3D%252522rapamycin%252Bholdings%252522%2526RS%3D%252522rapamycin%252Bholdings%252522&PageNum=&Rtype=&SectionNum=&idkey=610676BBEDCF

Just stop and think for a minute the profoundly altered paradigm of delivering simple raw powder systemically via widely used parenteral routes (my n=1) vs the insane amount of R&D spent on trying to engineer a better oral delivery rapamycin formulation. Of course, there is NO money in injection solution simple powdered rapamycin, so any startup/pharma needs IP, I get it commercially.

We’re talking about optimizing nature’s created rapamycin molecule (FDA approved 20+ years ago) for human longevity benefit. This should transcend human and commercial impediments…the door is wide open with properly formulated/dosed simple raw rapamycin powder parenteral delivery.

1 Like

The side effects at such LOW doses suggests indeed this nano-formulation had more bioavailability, although the AUC was quite low.

But the side effects on such low AUC…geez.

50% fatigue, 37.5% diarrhea, 25% oral pain, 25% dizziness. WHO WOULD WANT THIS???

These are relatively HEALTHY 68 yr olds…no chronic end stage disease transplant patients or metastatic cancer patients…so can we maybe dismiss that this cohort is in “ill health” re side effects?

Now on the PSA, very interesting indeed. The high dose cohort had a spike initially but then got crushed at 6 months? Sort of like my early parenteral delivery foray response…

My n=1 IM+IN experimentation…none of these side effects at orders of magnitude higher AUC levels? Is the 1st pass liver metabolism really the bad actor here?

1 Like

I’m going to try to find out from a compounding pharmacist.

Amazing that they got such favorable immune responses on such incredibly low weekly doses. Increasing naive T cells is very important in fighting cancer and infections. Since memory cells tend to be more prominent in the elderly and naive cells drop off, it leaves the aged more vulnerable. This is a significant finding and reinforces the idea that low weekly dosing is sufficient for enhanced immunity.

1 Like

Related research:

Overall, these data support the hypothesis that blocking mTORC1 signaling and/or tissue inflammation can effectively inhibit prostate cancer progression in a relevant mouse model of human prostate cancer. Furthermore, combinatorial approaches that target both pathways may be highly effective for prevention of prostate cancer progression in men.

Effect of Metformin, Rapamycin, and Their Combination on Growth and Progression of Prostate Tumors in HiMyc Mice

What we repeatedly see with cancer prevention is a combination of mTOR and inflammatory inhibition.
I suspect the same is true in all age related illnesses. With cardiovascular disease in particular, long telomere lengths seem to be associated with protection in multiple studies. So a telomerase activator may be of interest in that situation along with rapamycin and anti inflammatories.
I have a whole slew of anti inflammatory agents and don’t need to go to metformin for that purpose.

1 Like

The PSA response to the higher dose doesn’t make much sense. I’d say that cancer cells were initially dying and raising the psa but that doesn’t add up since rapamycin isn’t cytotoxic like that as far as I know.

1 Like

The compounding pharmacist says that eRapa isn’t FDA approved outside of clinical trials in the US.

1 Like