The battle against aging is being waged on two fronts.
One is the traditional approach of treating specific illnesses and failures as they arise: Helping people with creaky knees or hips to continue walking will keep them healthier.
This is the “replacement parts” approach, in the words of Mark Fishman, president of the Novartis Institutes for BioMedical Research, the research arm of the giant Swiss drug company.
Then there is the “extended warranty” strategy, as he calls it: delaying diseases such as cancer, diabetes, and Alzheimer’s in order to keep people alive and healthy longer.
Fishman’s boss, Novartis CEO Joseph Jimenez, has said he wants his company to lead the industry’s research into anti-aging strategies, a pledge that cheered patient advocates.
“I think it’s great to see pharma companies think more about aging,” said Brian Kennedy, chief executive of the Buck Institute, a California anti-aging research organization. “Others are talking about it. Novartis is the first.”
Among Novartis’s efforts on “replacement parts” are drugs under development to treat eye disease, hearing loss, damaged cartilage, and weakening muscles.
“The spare parts piece is a little more tractable within the lifetime of a pharmaceutical company,” Fishman said.
As part of the extended-warranty approach, Novartis is exploring whether an existing medicine can be repurposed to keep the body’s immune system from weakening and potentially extend healthy life. Much of Novartis’s research is conducted in Cambridge, at the company’s Institutes for BioMedical Research.
But this broader effort has its own challenges, and not just in the lab. For one, the pharmaceutical industry has not figured out how to get the Food and Drug Administration to authorize drugs that target an overall condition like aging, whose symptoms are not at a diagnosable or acute stage.
Yet people in the industry say the idea itself — being able to extend healthy life with drugs — is not that far off.
“Aging has been delayed in many, many labs,” said Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York. “The proof of concept has been achieved.”
Several commonly used medicines — aspirin, ibuprofen, and the diabetes drug metformin — have shown life-extending properties in animal studies. But they also have side effects, and researchers do not recommend taking them specifically to slow aging.
Normally, as people age, their ability to mount an immune response declines, even limiting the effectiveness of vaccines. But in a December study in Science Translational Medicine, Novartis showed that its kidney cancer drug everolimus, given with the flu shot, boosted the effectiveness of the flu shot. If the drug can help counter the immune system’s natural decline, it might win Food and Drug Administration approval to be administered in combination with vaccines.
Back on the “spare parts” front, both Novartis and Genentech are developing drugs to treat a form of eye disease known as dry macular degeneration. Both drugs aim to block the inflammation that can lead to the disease. Novartis’s drug has begun the early stages of human trials; it would be administered by a shot to the eye.
“Where you have to block and what’s the best way to block remains to be determined,” Fishman said of the eye treatment.
Hearing loss is another common symptom of aging. One cause is longtime exposure to loud noises that kill the tiny hairlike cells in the ear whose motion allows us to hear. The body cannot replace those cells naturally, so the more that are killed, the worse hearing becomes. Novartis is exploring whether the injection of a gene called Atonal 1 into the ear will turn regular cells into the hairlike ones.
“Even cooler is the fact that the nerve cells . . . reconnect up and in animal studies reestablish hearing,” Fishman said.
Many older people feel the effects of aging on their joints with every movement. For knees, for example, Novartis has discovered an agent that in animal studies may help torn and worn cartilage rebuild to original form. It is not clear yet how often the drug will need to be administered.
“In animals, one shot [in the knee] seems to do it for quite a while,” said Ronenn Roubenoff, a former professor at Tufts University who is now a researcher for Novartis. “But animals tend to heal faster than humans, especially humans over age 40.”
Muscle loss can quickly undermine an older person’s independence and lead to other problems. Drug companies Eli Lilly and Co. and Regeneron Pharmaceuticals are trying to develop a treatment to promote muscle growth by blocking a protein called myostatin.
Novartis is hoping that its own drug will be even more effective at strengthening muscles. In a paper Roubenoff and other Boston researchers published in December in the scientific journal Neurology, the drug was shown to restore thigh muscle volume for a small number of patients with the inclusion body myositis, a rare muscle disease. The company is in late-stage testing of the drug.
Roubenoff said his overall goal is not to prevent aging, but to prevent the disabilities that people get as they age.
“We want to focus on the folks who are at the limit of what they can handle, and where we can really make a difference,” Roubenoff said.Karen Weintraub can be reached at firstname.lastname@example.org.
Correction: Because of a reporting error, Novartis’ Chief Executive Officer Joseph Jimenez was misidentified in an earlier version of this story.