Rapamycin: a quick hisTORy
Quick overview of what you’ll learn from this blog post:
• What is rapamycin?
• A brief summary of the fascinating story behind its discovery
• What is mTOR?
• How rapamycin was identified as an mTOR inhibitor
• Overview of what rapamycin has shown in studies
• Why you may consider enrolling in (or donating to) AgelessRx’s rapamycin clinical trial
In the middle of the South Pacific Ocean, some 1300 miles from its nearest inhabited neighbor, lies the tiny remote island of Rapa Nui, or Easter Island, famous for its 800+ monolithic human statues called ‘moai’.
But incredible as the moai statues are, something potentially even more amazing can be found there too – the compound now known as rapamycin. In fact, the ‘rapa’ in rapamycin, comes from ‘Rapa’ Nui.
Yes to horses, nay to tetanus
During an expedition to Rapa Nui in 1964, Georges Nógrády and his team of fellow scientists were puzzled as to why the island’s inhabitants didn’t ever seem to get tetanus, even though they were constantly walking around barefoot, and there were lots of horses on the island. (Wherever there’s horses, there’s usually tetanus.)
The scientists divided the island up into 67 parcels, and took a soil sample from each, placing each sample in a small vial. These vials eventually ended up at Ayerst Pharmaceuticals in Montreal, where five years later in 1969, it was discovered that one of the samples contained a bacterium with the ability to produce rapamycin, a then-unknown compound.
Fast forward to the late 80s, and scientists were studying rapamycin and ‘rapalogs’ (compounds with similar structures to rapamycin) as powerful immunosuppressants for organ transplant recipients.
Let’s TORC about mTOR
In 1993 and 1994, multiple independent labs made breakthroughs in quick succession that led to a big discovery. Namely that rapamycin acts on a highly-conserved, previously unknown protein complex now known as mTOR, and that mTOR has two parts to it – mTORC1 and mTORC2.
One of the scientists working on these discoveries was David Sabatini, whose nickname in the scientific world these days is ‘mTOR man’. Dr Sabatini has done some excellent podcasts and presentations on mTOR and its discovery, and if you’re interested, we highly recommend you check them out.
What has rapamycin shown so far?
Although rapamycin has been approved by the FDA since 1994 for preventing organ rejection, its ability to address other diseases is still being researched. With this in mind, we thought we’d quickly outline some of the benefits rapamycin has already shown in both human and animal studies.
In 2009, rapamycin was the first molecule proven to extend the lifespan of a mammal, even when given late in life. (Harrison, D., Miller, R., et al.)
In 2010, rapamcyin eliminated cognitive deficits and reduced amyloid-beta in a mouse model of Alzheimer's. (Spilman, P., Galvan, V., et al.)
In 2014, rapamycin was shown to boost the human immune system. (Mannick, J., Klickstein, L., et al.)
In 2020, rapamycin rejuvenated oral health in aging mice. (An, J., Kaeberlein, M., et al.)
Thanks to this very promising animal and human data, there are currently over 200 ongoing human clinical trials of rapamycin registered at clinicaltrials.gov and at AgelessRx, we will soon be conducting a rapamycin clinical trial of our own, called PEARL. Read on to learn more about this extremely exciting initiative.
Gleaning PEARLs of wisdom
At AgelessRx, we believe the data thus far strongly supports further research into rapamycin as a way to slow down human aging, and for that reason, we will soon be conducting a clinical trial into the effects of rapamycin on longevity, in partnership with doctors at the University of California, Los Angeles.
Our trial will be named PEARL – Participatory Evaluation of Aging with Rapamycin for Longevity – and Dr. James P Watson at UCLA will be the principal investigator.
PEARL will be a low-cost, double-blind, randomized, placebo-controlled trial funded by patients and donations. Notably, it will be the first nationwide telemedicine trial in the US, and the first large-scale intervention trial on longevity with 200-400 adults 50+ taking part.
Interested in joining PEARL?
When taken in small doses, rapamycin has an excellent safety profile, and many people have given anecdotal evidence of rapamycin helping with everything from autoimmune conditions to arthritis and much more.
If you’re interested in learning more or taking part in our PEARL clinical trial, click here.