One of today’s most promising drugs for targeting aging has a long, circuitous history. In 1999, the US Food and Drug Administration approved rapamycin as an immunosuppressant to prevent the rejection of transplanted organs. Scientists later found it affected all sorts of biological processes; the “mammalian target of rapamycin” (or mTOR) includes immune function and inflammation.
Experiments also showed that rapamycin extended the life span of yeast, worms, and mice. Could it do the same thing in humans?
At present, there’s no rigorous way to test rapamycin’s potential to slow human aging. Rather, researchers have zeroed in on a significant aspect of aging—the decline in immune function—to see if drugs that mimic rapamycin can enhance immune function in older people.
Joan B. Mannick is cofounder and chief medical officer of a biotech company called resTORbio, spun out of Novartis in 2017, which is conducting clinical trials of RTB101. It’s a drug candidate at the forefront of efforts to slow the age-related decline of the immune response. Mannick says we will have our first answer about the potential of this anti-aging intervention within a year.
Q: In 2009, experiments showed that molecules blocking the rapamycin pathway extended life span in lab animals. Were you following that work?
A: Yes. Around that time, in 2010, I went to Novartis in what’s called their New Indications Discovery Unit. In that unit, we were allowed to choose indications that didn’t fall into traditional Big Pharma buckets and so might be missed in drug development. The area that I wanted to work in was aging. I proposed to Novartis that I would look at the effects of Novartis’s rapamycin analogue, a cancer drug, on an aging-related condition in humans.
Q: Why did you choose immune function? And why that particular patient population, in New Zealand and Australia?
A: We had to think about: What is an aging-related endpoint that we can assess in a relatively short period of time in a clinical trial? What we decided to study first was immune function. When old animals are given TORC1 inhibitors [drugs that block the TOR pathway], there’s some data that their immune function gets better, and they respond better to an influenza vaccination. In the first study, the first thing we chose to do was just say: Can older people respond better to an influenza vaccination when they’re given a TORC1 inhibitor? At the time that we were running this trial, it was cold and flu season in the Southern Hemisphere, in Australia and New Zealand.