It was one of the most mind-bending scientific reports in 2014: Injecting old mice with the plasma portion of blood from young mice seemed to improve the elderly rodents’ memory and ability to learn. Inspired by such findings, a startup company has now launched the first clinical trial in the United States to test the antiaging benefits of young blood in relatively healthy people. But there's a big caveat: It's a pay-to-participate trial, a type that has raised ethical concerns before, most recently in the stem cell field.
The firm’s co-founder and trial principal investigator is a 31-year-old physician named Jesse Karmazin. His company, Ambrosia in Monterey, California, plans to charge participants $8000 for lab tests and a one-time treatment with young plasma. The volunteers don’t have to be sick or even particularly aged—the trial is open to anyone 35 and older. Karmazin notes that the study passed ethical review and argues that it’s not that unusual to charge people to participate in clinical trials.
To some ethicists and researchers, however, the trial raises red flags, both for its cost to participants and for a design that they say is unlikely to deliver much science. “There's just no clinical evidence [that the treatment will be beneficial], and you're basically abusing people's trust and the public excitement around this,” says neuroscientist Tony Wyss-Coray of Stanford University in Palo Alto, California, who led the 2014 young plasma study in mice.
Decades ago, so-called parabiosis studies, in which the circulation of old and young animals was connected so that their blood mingles, suggested that young blood can rejuvenate aging mice. A recent revival of the unusual approach has shown beneficial effects on muscle, the heart, brain, and other organs, and some researchers are scrutinizing young blood for specific factors that explain these observations. The 2014 study, however, suggested that repeated injections of plasma from young animals were an easy alternative to parabiosis. Wyss-Coray has since started a company, Alkahest, that, with Stanford, has launched a study of young plasma in 18 people with Alzheimer’s disease, evaluating its safety and monitoring whether the treatment relieves any cognitive problems or other symptoms. The company covers the participants’ costs. Wyss-Coray expects results by the end of this year. (Another trial at a research hospital in South Korea is examining whether cord blood or plasma can prevent frailty in the elderly.)
In Ambrosia’s trial, 600 people age 35 and older would receive plasma from a donor under age 25, according to the description registered on ClinicalTrials.gov, the federal website intended to track human trials and their results. Karmazin says each person will receive roughly 1.5 liters over 2 days. Before the infusions and 1 month after, their blood will be tested for more than 100 biomarkers that may vary with age, from hemoglobin level to inflammation markers. The $8000 fee—not mentioned on ClinicalTrials.gov—will cover costs such as plasma from a blood bank, lab tests, the ethics review, insurance, and an administrative fee, Karmazin says. “It adds up fairly quickly.”
Kamarzin became interested in aging as an undergraduate. In medical school at Stanford, where he rotated through labs focused on stem cells and aging, he took note of the young plasma mouse study and other parabiosis research. Karmazin was also intrigued by the story of a Russian physician named Alexander Bogdanov, who in the 1920s gave himself infusions of young human blood that he claimed boosted his energy level and bestowed a more youthful appearance. There are “overwhelming data” suggesting that young plasma will be beneficial to people, Karmazin says.
Last year, Karmazin co-founded a company called xVitality Sciences that aimed to offer plasma treatments at clinics overseas. The venture didn’t pan out—Karmazin left, and the company is now apparently defunct. Karmazin then started Ambrosia with Craig Wright, a former chief scientific officer at a vaccine company, who now runs a clinic in Monterey. The company’s study, which was reviewed by a commercial ethics board used by some for-profit stem cell clinics, doesn’t need approval by the U.S. Food and Drug Administration, the pair says, because plasma transfusions are a well-established, standard treatment. Karmazin says he and Wright have now heard from about 20 prospective participants, and have enrolled three, all elderly. Wright will likely transfuse plasma into the first person in late August.
To bioethicist Leigh Turner at the University of Minnesota, Twin Cities, the study brings to mind a growing number of scientifically dubious trials registered in ClinicalTrials.gov by private, for-profit stem cell clinics. The presence of such trials in the database confers “undeserved legitimacy,” he says.
The scientific design of the trial is drawing concerns as well. “I don’t see how it will be in any way informative or convincing,” says aging biologist Matt Kaeberlein of the University of Washington, Seattle. The participants won’t necessarily be elderly, making it hard to see any effects, and there are no well-accepted biomarkers of aging in blood, he says. “If you’re interested in science,” Wyss-Coray adds, why doesn’t such a large trial include a placebo arm? Karmazin says he can’t expect people to pay knowing they may get a placebo. With physiological measurements taken before and after treatment, each person will serve as their own control, he explains.
Doubts aside, Ambrosia’s trial has already attracted attention from the investment company of billionaire Peter Thiel, who is apparently interested in trying young plasma treatments himself, Inc. reported today. Karmazin says he’s filling a void, suggesting that most companies wouldn’t be interested in developing human plasma as an antiaging treatment. “It’s this extremely abundant therapeutic that's just sitting in blood banks,” he insists.
*Correction, 2 August, 10:23 a.m.: This story has been corrected to clarify that it is the enrolled patients in the study who are elderly.
View our related Science in the Classroom annotated research paper on rejuvenation of the aging mouse brain.