This Anti-Aging Injection Might Actually Work
This Anti-Aging Injection Might Actually Work

Stem cells are overhyped as a cure for everything. But they‘re finally showing promise in making elderly people stronger.

Illustration by Thomas Hedger

Phillip George golfs regularly, works out on a treadmill, and lifts a few weights — “not body building, just toning,” he says. Now in his 70s, the retired plastic surgeon used to get achy if he overdid it at the gym or the golf course, and often popped a few Advil or Tylenol.

But George cut way back on the painkillers two years ago, after becoming one of the first patients to try a new tactic to slow aging. As part of a clinical trial led by University of Miami cardiologist Joshua Hare, George got an infusion of millions of someone else’s stem cells, the kind of multi-purpose cells that can form other types of cells. “The pain diminished dramatically,” George says.

There are a lot of doctors who promise cures from stem cells. Hare isn’t one of them. At least not yet.

Nevertheless, after spending his career investigating what stem cells can do for the body, Hare thinks he’s hit upon a way to reduce frailty, boost the immune system and heart, and maybe even fight off Alzheimer’s: by giving patients large doses of a certain kind of stem cell.

His approach hasn’t been proven to work yet, but a review of clinical trials and discussions with scientists suggest that Hare is closer than anyone else to using stem cells to address problems caused by aging.

Although stem cells are considered an incredibly promising area of research, the procedures that have been definitively shown to work are ones that have existed for decades, such as bone marrow transplants and similar interventions for cancer and some blood diseases. No new treatments using the cells have been proven to be medically effective.

It’s not for a lack of trying: the National Library of Medicine lists about 1,700 ongoing studies involving stem cell treatments. But companies that sell treatments for everything from knee pain to autism and heart disease to Parkinson’s disease do not yet have scientific proof in humans.

On top of that, stem cell therapy can be risky when sloppily delivered. Three older women were blinded by a treatment intended to reverse their vision loss, according to a report last year in the New England Journal of Medicine. Many others, including professional athletes and celebrities, have spent tens of thousands of dollars for treatments that have not been shown to be any more effective than placebo. In stepping up its enforcement against unscrupulous clinics last year, the U.S. Food and Drug Administration warned consumers to avoid stem cell therapies that are not FDA-approved, unless they are part of a registered research trial.

“You can really consider them to be these miniature drug-delivery factories.”

That was the case when Phillip George got his infusion two years ago. He was in the first clinical trial to test these cells as a treatment for aging-related frailty. He says the infusion wasn’t painful, and he doesn’t think he took any kind of a risk, even though the procedure had been tried on only about 100 people before him. George also had known Hare for 11 years, since he was on the hiring team that brought the younger doctor to Miami.

So far, so good, George says: “Two years into the process, I don’t see or recognize any negatives from it.”

Regeneration

Your supply of stem cells naturally falls with age. This makes it harder for the body to repair damage, and can lead to inflammation. Inflammation, in turn, undergirds many of the problems we associate with old age, including frailty, heart disease, immune weakness, and Alzheimer’s, says Anthony Oliva, senior scientist at Longeveron, the privately held Miami company that Hare started to bring his ideas to market.

Joshua Hare

Longeveron uses mesenchymal stem cells, which come from bone marrow. They are known to be involved in regulating and sometimes reducing inflammation, as well as in helping to boost repair mechanisms for blood vessels. They may also prompt the body’s own stem cells to get more active in beneficial ways. There are currently 817 studies worldwide investigating the use of mesenchymal stem cells in people, for everything from knee injuries to ulcerative colitis, according to the federal government’s ClinicalTrials.gov. Mesenchymal stem cells are being tested in cats to see if they can reduce feline inflammation.

“You can really consider them to be these miniature drug-delivery factories,” Oliva says, describing mesenchymal stem cells as almost miraculous. “They can last for many months inside the recipient. They’re homing to the site of inflammation and damage. They are decreasing inflammation. They’re promoting improvement of the vasculature. They’re stimulating intrinsic stem cells to repair and regenerate over months.”

Hare’s research has cataloged how an objective measure of inflammation, the cell-signaling protein TNF-alpha, falls after an infusion of mesenchymal stem cells. In both animals and people, Hare says, the protein level remains lower for six to 12 months.

The cells also appear to be safe. “Working in medicine 30 years, I’ve never seen anything this well tolerated,” Hare says.

The immune system doesn’t react to these donor stem cells because it essentially doesn’t see them, Oliva says. Most cells in the body express a protein called MHC class II on their surface. The protein acts like a flag to alert the body to something foreign. In an organ transplant, the patient’s MHC class II has to match the donor’s to reduce chances of rejection. But mesenchymal stem cells don’t have these flags.

Longeveron uses cells from young donors, who are paid a small stipend and have been screened three times for diseases like HIV, hepatitis, and Zika, Oliva says. Their mesenchymal stem cells are extracted in a far less painful way than you might imagine, with just local anesthesia, a single needle stick, and a Band-Aid to cover the spot.

Longeveron then cultures the cells—putting them in a fluid to make them proliferate—before infusing them into a patient. For now, one donor can supply tens of patients, but Hare hopes to improve the culturing process so that one donor can provide enough cells for several hundred doses. If the company’s trials persuade regulators to approve the therapy, “we’re going to have a very large market and a very significant need,” he says.

A mysterious result

For its frailty research, Longeveron is now running a phase 2b trial — roughly the midpoint of the clinical trial process. It has tested its cells in about 20 out of 120 patients so far, says Suzanne Page, the chief operating officer.

Longeveron also has an early trial comparing the donor cells versus a placebo in a small number of patients with Alzheimer’s disease; another trial looking at frail patients’ resistance to the flu virus after receiving the donor cells compared to placebo; and a fourth looking at metabolic syndrome. Hare is also conducting a study checking back with patients who received stem cell treatments years ago for heart conditions.

To treat organ damage, like a heart attack that leaves a scar in the heart muscle, stem cells probably have to be injected directly into the organ, Hare says. But for a systemic, aging-related condition like frailty, the cells can be infused into the bloodstream because they tend to “traffic to inflamed areas,” he says.

If further trials confirm Longeveron’s approach, “we’re going to have a very large market,” Hare says.

Longeveron’s first published study on frailty showed that patients such as George, who received 100 million mesenchymal stem cells, showed “remarkable improvements in physical performance measures and inflammatory biomarkers.” The average age of the patients was 75.5.

Oddly, the patients who received a double dose of 200 million donor cells did not see any benefit at all. And that result fuels the concerns that molecular biologist Andrew Mendelsohn has about the research.

Mesenchymal stem cells have been the subject of hundreds of clinical trials, notes Mendelsohn, who wrote a commentary about Longeveron’s experiment in the journal Rejuvenation Research. Some studies show improvements, some don’t. When the studies are repeated, their results are inconsistent.

“If you do the experiment in mice, you see all kinds of great results. When you get to people you get all kinds of mixed results,” says Mendelsohn, director of molecular biology for the Panorama Research Institute, a privately owned biomedical research and development holding company in Sunnyvale, California.

Mendelsohn says he thinks Hare’s research has promise. But he won’t be convinced, he says, until he sees clear evidence in repeated clinical trials. “I have a strong belief that eventually it can be engineered to work out, even if it’s not nearly as effective as we might like it to be,” Mendelsohn says.

Paul Knoepfler, a biologist and stem cell scientist at the UC Davis School of Medicine, says he too is troubled by the inconsistent results of stem cell studies, and by the therapy’s relatively modest benefits.

Other research suggests to him that donor mesenchymal stem cells don’t stay in the body for very long, contrary to what Oliva says about how they last for months. Knoepfler is not sure how patients could have a long-term benefit if the body clears out the cells within a week or so.

Furthermore, frailty and other age-related processes are complicated. They’re not caused by one trigger and they probably can’t be fixed by one type of treatment, Knoepfler says.

Even so, he considers Hare’s work worthwhile and says it’s being conducted responsibly. “I don’t see any red flags,” Knoepfler says. “It’s just sort of early days.”

Phillip George acknowledges that the benefits he saw might have been caused by a placebo effect. But he’s still signed up to get a second infusion of the cells, part of a test of whether it can be given multiple times without harm.

“I’m not a Pollyanna. I’m not jumping at the first of everything,” George says. But if he has the opportunity to benefit from a potentially exciting new treatment, if there’s no apparent downside, and if he can benefit science in the process, then why not try?
['Karen Weintraub']
['Technology', 'Longevity', 'Aging', 'Stem Cell Research', 'Biotechnology']