A drug that was first approved by the FDA for use in transplant patients in the late 1990s is being prescribed off-label by some physicians with the aim of fending off age-related conditions.
Thus far, personal reports are that it works, and now a dentist has been granted FDA approval to test rapamycin in patients with gum disease – a common condition that tends to accelerate with age – measuring changes in participants’ microbiomes and their biological clocks at the same time.
A few years back, US biologist Matt Kaeberlein was diagnosed with a frozen shoulder. “It was really bad,” he recalls. He wasn’t sleeping well and and his doctor recommended physical therapy, saying it could take a year to get better.
Feeling frustrated, he decided to try rapamycin, which so far has been untested in people taking it for anti-ageing, but has been shown to extend the lifespan of mice.
Kaeberlein said it was his “first foray into biohacking”. He was very pleased with what happened next.
“Within two weeks, 50% of the pain had gone,” he says. And by the end of 10 weeks, he had regained range of motion and the pain was completely gone.
“It hasn’t come back,” he told NPR.
Kaeberlein is no stranger to rapamycin – he is co-founder of the Dog Ageing Project to study how rapamycin influences dogs’ healthspans. He’s also the former director of the Healthy Ageing and Longevity Research Institute at the University of Washington.
Rapamycin was first given the green light by the FDA for use in transplant patients in the late 1990s. At high doses it suppresses the immune system. At low doses, Kaeberlein says it seems to help tamp down inflammation. It works by inhibiting a signalling pathway in the body called mTOR, which seems to be a key regulator of lifespan and ageing.
Despite the drug not being approved for pain or anti-ageing, some physicians prescribe it with the aim of fending off age-related conditions. Kaeberlein and his colleagues surveyed about 300 of these patients, who take low doses, and many report benefits.
But anecdotes are no replacement for science. To figure out the risks and benefits of a drug, research is needed. And that’s where a dentist comes in.
Dr Jonathan An, at the University of Washington, has been granted FDA approval to test rapamycin in patients with gum disease, which is a common condition that frequently accelerates with age.
When he treats patients with gum disease, he says there’s not much he can do beyond cleaning and removing the plaque – a build-up of bacteria.
“All we’re doing is putting a bandage on,” he says. His goal is to find and treat the underlying cause of the disease.
There’s already some evidence from transplant patients that rapamycin may help improve oral health.
And as part of the study, An and his collaborators will also measure changes in participants’ microbiomes and their biological clocks.
The study will enrol participants over 50 who have gum disease. They will take the drug, at various doses, intermittently for eight weeks. Then, An will be able to determine if the drug is safe and effective.
If rapamycin has a beneficial effect, he says, it will help demonstrate that it’s possible to target the root cause of the disease. “It really comes down to targeting the biology of ageing,” he says.
He thinks gum disease may be a kind of canary in the coalmine of age-related diseases. For instance, gum disease is linked to a higher risk of heart disease, and maybe dementia, too.
Scientists say it’s possible that bacteria in the mouth linked to periodontal disease causes inflammation, which may cause a “cascade” of damage to blood vessels, leading to problems in the heart or brain.
“If we can target that underlying biology, we predict that it might address a lot of these other underlying conditions,” An says.
Rapamycin is a generic drug, so pharmaceutical companies have little incentive to fund new research. An and his collaborators have received a grant to conduct the trial, which could open the door to further studies to determine whether rapamycin can help prevent or slow down other age-related diseases.
Eric Verdin, a physician who heads the Buck Institute for Research on Ageing, says his group is fundraising for more research on rapamycin. He says there are a lot of unanswered questions, for example, “what is the effect of different concentrations in a single dose?”
And he wants to look for a “molecular signature” in people taking rapamycin. He wants to know more about doses and intervals, since many doctors prescribing it off-label recommend cycling on and off the drug.
Researchers are also working on other drugs that may work in similar ways, and there’s a push for new drugs – or other interventions that target biological aging, including a new $100m XPRIZE Healthspan competition, aimed at accelerating the research in the field supported by Hevolution and other funders.
NPR article – Rapamycin may slow ageing. Here's one way the drug will be tested (Open access)
See more from MedicalBrief archives:
General health improved by treating periodontal disease
DNA-evidence shows link between gingivitis and Alzheimer’s
Cheap diabetes drug may delay ageing, say US scientists
Is ageing without illness possible?