#502 What the Most Promising Longevity Drug Did for Humans - Dr. Brad Stanfield

Brad Stanfield (0:00)

A 75-year-old doesn't get as much benefit from exercise compared to a 25-year-old. We were hoping that if we could get the dose of rapamycin correct, that we would be able to somewhat treat that, as in that 75-year-old hopefully would get maybe not as much benefit, but almost as much benefit from exercise as that 25-year-old. You know, with coronary heart disease, that's essentially a solved problem. With all of the, you know, remedies that we've got now, and the things that we can prescribe, and, you know, diet, exercise, sleep, all those good things, it's essentially a solved problem. And if you look at things like obesity, that's rapidly becoming a solved problem. One of the gains that we haven't yet mastered is muscle health.

Siim Land (0:37)

Right, welcome back to the show.

Brad Stanfield (0:39)

Yeah, great to be here. Thanks for your time.

Siim Land (0:41)

Yeah, we recently had our panel discussion with Matt Kaberlein and Michael Lusgarden about blood work, but you since then published your reprimising trial, which you crowdfunded and recently just finished. So I'm excited to talk about it and see what can we learn about reprimising from the trial and just the general longevity and aging.

Maybe we can start with what made you interested in researching reprimising this way.

Brad Stanfield (1:17)

Yeah. So in the preclinical models, whenever it's tested in worms, flies, mice, it extends lifespan. So the interventions testing program, when they trial it, they get about 20 to 25 percent lifespan extension in both male and female mice. So the effect size is huge and it's quite cool that it works in both males and females. But in clinical medicine, it's got a bit of a dirty name. It's an immunosuppressant that's used to prevent your body from rejecting a donated organ. So if you needed a kidney transplant, for instance, one of the drugs that you'd most likely be on is rapamycin to dampen down your immune system and again, make sure that you don't attack that donated organ. So there's been a reluctance within the medical community to trial it in otherwise healthy individuals. Not only that, there's no money to be made here because rapamycin was discovered in the 1960s. So it's off-patent, there are generics available. So Big Pharma is not going to fund this type of research. So when I was looking at what impact we could make within the research field, where were the areas that weren't being looked at, rapamycin seemed like a really interesting case. So I was thinking at the time, and this was about five years ago that I started actually mentioning that I wanted to do this study. So it's been a long journey.

What could we do as a community to make the biggest difference for everyone's health? So yeah, rapamycin seemed to be the one to go for.

Siim Land (2:41)

Yeah, the rapamycin is always said to be the biggest potential for life extension in humans as well that gets talked about.

And yeah, I mean, there's no obviously long-term human studies to know if it does extend lifespan, but you can see short-term changes in various biomarkers and other aspects of health and aging that at least would tell you some future, I guess, predictions, whether it will have any long-term health impacts. But yeah, I mean, we can maybe first start with what was your idea going into, your hypothesis going into it and what it defined, and then we can discuss about the details of the findings.

Brad Stanfield (3:28)

So with rapamycin, if we tried to do a human lifespan study, we'd be waiting decades and you'd need hundreds and hundreds of patients to actually have the statistically significant results. So that wasn't really the study that I thought was going to work feasibly. So we were thinking what endpoints, as in what things should we measure that would actually be useful for patients sitting in front of me at the clinic, that have the potential to be improved because of rapamycin. And when we were going down this journey, one of the things that struck me is that there's human evidence showing that as human muscle gets older, it starts to overexpress mTOR complex 1 So mTOR complex 1, when it's activated, it drives protein synthesis.

But the trouble is, it's almost like our aged muscles, they're trying to compensate for becoming weaker, and they're trying to overexpress mTOR complex 1, to build up new proteins. The trouble is when you're doing that, you don't have time for another process to happen, which is autophagy, so the cell clearance process. So the idea was that old muscle is hoarding all of these damaged components, and if we could turn down mTOR complex 1 using rapamycin, we could allow autophagy to happen, and then we could have separate periods of time where we're ramping mTOR complex 1 back up with exercise. So that's kind of how the trial design came about, is that if we got people to exercise at home on day 1, day 3, and day 5, and then on day 6, if they took either rapamycin or placebo, then we could see if we could improve muscle performance over and above exercise alone. So once we kind of firmed up that trial design, then the big question was about fundraising. Because like I said, there's no money to be made here. So you can't pitch to investors to fund a trial like this. And the trial in total, it cost about $720,000 US dollars. So it's a significant financial undertaking. Now, I made two massive errors when I first tried to fundraise. I didn't realize how expensive it was going to be. I thought for a relatively small study of 40 participants over a 13-week time horizon, I was thinking that a trial might cost $150,000.