Experimental Drugs Boost Elderly Immune Systems, Raising Hopes For Anti-Aging Effects

7 hours ago
Originally published on July 11, 2018 8:51 pm

Scientists on the hunt for anti-aging drugs say they've made an advance with tantalizing potential: Two experimental drugs appear to safely boost the immune systems of elderly humans.

The researchers stress that more research is needed to confirm the findings and show the drugs are safe. And at least one researcher says the findings are based on a relatively small number of people and used methods that could produce misleading results.

Still, many researchers say the findings are encouraging.

"I think the results are quite exciting," says Felipe Sierra, director of the division of aging biology at the National Institute on Aging.

For the study, researchers tested very low doses of two drugs. One, called RAD001, is used to fight cancer and prevent rejection in organ transplant patients. The other, known as BEZ235, was developed as a cancer drug. Both drugs, known as TORC1 inhibitors, affect a crucial cellular pathway that plays a role in the immune system and other biological functions. Similar drugs were previously linked to extending the lifespans of lab animals.

Researchers think this pathway may prove key to developing future anti-aging treatments.

"It is possible that further research with this same combination of drugs or similar combinations will lead to a possibility of addressing multiple chronic diseases because these drugs have been shown to affect the process of aging itself," Sierra says.

Researchers gave 264 people age 65 or older various doses of one or two of these drugs, or a placebo, every day for six weeks. The researchers then followed them for a year to see if they reported fewer infections. They also tested how their immune systems responded to a flu vaccine.

"We decided to start by just looking at whether we could make immune function better because that's something that's relatively easy to measure in a short period of time," says Joan Mannick, chief medical officer at resTORbio, Inc., a Boston-based company. She conducted the research at the Novartis Institutes of Biomedical Research. It was published Wednesday in the journal Science Translational Medicine.

After a year, the study subjects who got the two-drug combination reported 1.49 infections, such as colds and bronchitis, the researchers report. Those who took the placebo reported 2.41 infections. That works out to be about a 40 percent reduction.

"That's a big reduction," Mannick says.

The drugs also boosted how the elderly study subjects' immune systems responded to a flu vaccine — increasing the levels of flu antibodies their immune systems produced by more than 20 percent, Mannick says.

That's significant because older people are among the most vulnerable to the flu. In addition, the vaccine often doesn't work as well on their older, weaker immune systems.

"Respiratory tract infections are the fourth leading cause of hospitalizations in people 65 and older and a major cause of death," Mannick says. "So if we can reproduce these findings ... that's a big deal."

The most common side effect of the drug was diarrhea, but that was usually relatively mild, the researchers say.

Even with the positive results, some researchers are trying to temper their colleagues' enthusiasm.

"It is premature, in my opinion, to rule out major negative effects of the pharmacological agents used in this study among sub-sets of human subjects," wrote George Martin, a professor emeritus of pathology at the University of Washington.

But other scientists say the results could help point the way toward successful therapies, building on years of research in this area.

Scientists have long known that severely restricting the intake of calories by organisms can extend their lifespans. Most people are unable to sustain severe caloric restriction for long periods, however. So scientists have been trying for years to find drugs that could produce the beneficial biological effects of caloric restriction.

The drug rapamycin generated excitement as one potential candidate. It was shown to extend the lifespans of lab animals, working on the same cellular pathway as caloric restriction. But that drug also raised safety concerns. As a result, scientists have been searching for alternatives that have the same benefits without the risks. The two drugs tested in the new study could be such drugs, the researchers say.

Aubrey de Grey, an aging researcher at the SENS Research Foundation in Mountain View, Calif., says that "perhaps the most exciting aspect of the results is that the protection lasted for the duration of the study, namely a year, even though the drug was only given for the first six weeks."

Mannick says her company has already started testing these drugs on sicker elderly people to try to get a better idea of how well they work and how safe they are, she says.

"This study is the first step to suggest we may be able to target some of the fundamental pathways contributing to aging to promote healthy aging, including healthy immune function, in older people," she says.

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AILSA CHANG, HOST:

Scientists on the hunt for anti-aging drugs say they may have made a tantalizing advance. They've shown that drugs, like those that can extend the lives of lab animals, appear to safely boost the immune systems of elderly humans. NPR health correspondent Rob Stein has the details.

ROB STEIN, BYLINE: One of the holy grails of medical research is finding ways to fight aging. Severely restricting how many calories someone consumes may do that, but that's not practical for most people. So scientists have been testing drugs that seem to help lab animals live longer by mimicking what severe caloric restriction does in the body.

JOAN MANNICK: If this translates to humans, humans will live healthier longer. And that's our goal - is to promote healthy aging.

STEIN: That's Joan Mannick, chief medical officer at a Boston company called resTORbio. Her team tested two drugs that appear to have these anti-aging powers.

MANNICK: And we decided to start by just looking at whether we could make immune function better 'cause that's something that's relatively easy to measure in a short period of time.

STEIN: They gave 264 elderly people one or two of these drugs or placebo every day for six weeks and followed them for a year. The drugs appear to reduce the number of infections by about 40 percent.

MANNICK: That's a big reduction.

STEIN: The drugs also boosted how the elderly people's immune systems responded to a flu vaccine. That's a big deal because older people are among the most vulnerable to the flu. And the vaccine often doesn't work as well on their older, weaker immune systems.

MANNICK: Respiratory tract infections are the fourth leading cause of hospitalizations in people 65 and older and, you know, a major cause of death. So if we can reproduce these findings - and they have to be reproduced and validated - that's a big deal.

STEIN: The drugs did cause some stomach problems for some people, but that was usually no big deal. And Mannick hopes these kinds of drugs may do more than just protect older people from infections.

MANNICK: This study is the first step to suggest we may be able to target some of the fundamental pathways contributing to aging - to promote healthy aging, including healthy immune function, in older people.

STEIN: Some experts caution that this study was relatively small and used methods that could produce misleading results, but others say the results are encouraging.

FELIPE SIERRA: I think the results are quite exciting.

STEIN: That's Felipe Sierra, director of the division of aging biology at the National Institute on Aging.

SIERRA: It is possible that further research in this same combination of drugs or similar combinations will lead to a possibility of addressing multiple chronic diseases because these drugs have been shown to affect the process of aging itself, which is a major risk factor for all of those diseases.

STEIN: The drug company has already started testing these drugs on more elderly people to try to get a better idea of how well they work and how safe they are. Rob Stein, NPR News.

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