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HomeBio-EthicsClinical trial with 'young blood' to slow ageing is labelled a 'scam'

Clinical trial with 'young blood' to slow ageing is labelled a 'scam'

YoungbloodA pay-to-participate private clinical trial on the potential of 'young' blood plasma from teenagers and young adults can reverse certain of the hallmarks of ageing, has been labelled a 'scam'.

Just off a winding highway along the Pacific coast in Monterey, California, is a private clinic where people can pay $8,000 to have their veins pumped with blood plasma from teenagers and young adults. MIT Technology Review reports that Jesse Karmazin is the entrepreneur who made the practice possible, by launching a clinical trial on the potential of “young blood” through his start-up Ambrosia. He says that within a month, most participants “see improvements” from the one-time infusion of a two-litre bagful of plasma, which is blood with the blood cells removed.

But the report quotes several scientists and clinicians as saying that Karmazin’s trial is so poorly designed it cannot hope to provide evidence about the effects of the transfusions. And some say the pay-to-participate study, with the potential to collect up to $4.8m from as many as 600 participants, amounts to a scam.

What is certain, the report says, is that it’s based on some intriguing if inconclusive science.

Karmazin, a 32-year-old Princeton graduate and competitive rower, says he was inspired by studies on mice that researchers had sewn together, with their veins conjoined, in a procedure called parabiosis.

Over the last decade or so, such studies have offered provocative clues that certain hallmarks of ageing can be reversed or accelerated when old mice get blood from young ones. Yet these studies have come to conflicting conclusions. An influential 2013 paper showed that a particular component in young blood, GDF11, increased muscle strength, for example, but other researchers could not replicate the finding. Further, parabiosis experiments offer little insight into how Ambrosia’s one-time transfusions will affect people. “In our study, circulation between the young and old mouse was maintained for nearly four weeks,” says Amy Wagers, a professor of regenerative biology at Harvard University and an author on the report.

Despite such uncertainties, the report says the potential of young blood to treat disease is being explored in a number of clinical trials. One test sponsored by the University of California – San Francisco, is examining the effects of transfusions in patients with a degenerative disorder called progressive supra-nuclear palsy. A study under way in China investigates whether young plasma alleviates the neurologic deficits induced by acute stroke.

In 2014, Stanford University neuroscientist Tony Wyss-Coray demonstrated that old mice had increased neuron growth and improved memory after about 10 infusions of blood from young mice. That prompted Wyss-Coray to launch a small company, Alkahest, based in Menlo Park, California, to test transfusions of plasma from young people in the treatment of Alzheimer’s disease.

The report says Alkahest’s clinical study is more conventional than Ambrosia’s: it does not charge participants, it expects to enrol only 18 volunteers, and it is initially looking at how well the elderly can tolerate small doses of plasma. Wyss-Coray says the company’s initial funding was provided by a billionaire in Hong Kong who felt that a plasma transfusion had helped his grandfather combat Alzheimer’s. In March 2015, the plasma company Grifols invested $37.5m in the start-up.

The report says like several other researchers and bioethicists, Wyss-Coray worries about the fact that Ambrosia’s trial is funded by participants rather than investors. “People want to believe that young blood restores youth, even though we don’t have evidence that it works in humans and we don’t understand the mechanism of how mice look younger,” Wyss-Coray says. “I think people are just attracted to it because of vampire stories.” He mentions a Hungarian tale of a wealthy woman who bathed in the blood of virgins to retain her youth.

But, the report says, Karmazin shares none of this hesitancy. “I think the animal and retrospective data is compelling, and I want this treatment to be available to people,” he says. He named his startup Ambrosia after the food of the immortal gods in Greek myth.

With an MD but no license to practice medicine, Karmazin is conducting the trial with David C Wright, a 66-year-old physician with a private intravenous-therapy centre in Monterey. According to the report, Wright offers “alternative” IV infusions of antibiotics, vitamins, and other treatments; they’re popular among people suffering from conditions with nebulous symptoms, such as chronic fatigue syndrome or “chronic” Lyme disease. In January 2015, he was disciplined by the California Medical Board for administering antibiotic infusions to a patient who didn’t need them and ended up in an emergency room. The report says Wright did not respond to phone calls.

As of 15 December, Karmazin says, Wright had infused 25 people with young blood. Karmazin claims his participants are seeing miraculous results; a patient with chronic fatigue syndrome, for example, “feels healthy for the first time” and “looks younger.”

The report says such anecdotes could help market the study, but they’re no proof the plasma infusions work, and would-be patients shouldn’t believe them.

“There are a lot of patient-funded trials run by companies that use the trials as a way to sell products that wouldn’t be marketable because they’d have to be regulated by the FDA,” says Jonathan Kimmelman, a bioethicist at McGill University in Montreal.

The formal goal of the Ambrosia study is to measure the effect of young plasma on about 100 biomarkers. Before the infusion, and one month after, all participants have their blood analysed for biomarkers that include everything from hemoglobin to leptin. But Irina Conboy, a professor at the University of California – Berkeley, thinks the biomarker results will be meaningless: for one thing, the study lacks a control arm with patients who don’t get plasma.

Blood biomarkers, she says, change for many reasons. “If you eat a meal, leptin changes,” she says. She’s also wary of Alkhest’s study on Alzheimer’s patients. Last year, she and colleagues found that older mice whose blood was partially replaced with younger blood saw few benefits. “Both studies are hurt by the same problem, and the problem is that there is no evidence to suggest that an infusion of plasma from young to old animals reverses aging,” she says.

Conboy says in the report that despite that, many people are willing to avail themselves of questionable anti-ageing remedies. “You’ll see them at some meetings – people in the audience who open satchels of strange food,” she says. “That is the group that Ambrosia is preying upon.”

Ambrosia says it will enrol almost anyone over 35, and the fees of $8,000 per person could add up. But Karmazin rejects the idea he is out to generate profits. He says that money is needed to cover the cost of clinical procedures, laboratory tests, and the plasma. Publicly available prices suggest that two litres of plasma could cost roughly $1,000, and a single run-down of biomarkers another $3,000 or so. He adds that because patients are paying it wouldn't be fair to give anyone a placebo.

The report says risk is the ultimate question when it comes to the ethics of Ambrosia’s trial. Although blood transfusions are considered safe for people who need them to survive, side effects can include hives, lung injury, or even deadly infections.

Dobri Kiprov, chief of the immunotherapy division at California Pacific Medical Centre in San Francisco, says he has met several people who express interest in Ambrosia’s trial. He tries to dissuade them. “To expose people to danger unnecessarily – in my mind, that is really horrible,” he says.

The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGF-β superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging.

Francesco S Loffredo, Matthew L Steinhauser, Steven M Jay, Joseph Gannon, James R Pancoast, Pratyusha Yalamanchi, Manisha Sinha, Claudia Dall’Osso, Danika Khong, Jennifer L Shadrach, Christine M Miller, Britta S Singer, Alex Stewart, Nikolaos Psychogios, Robert E Gerszten, Adam J Hartigan, Mi-Jeong Kim, Thomas Serwold, Amy J Wagers, Richard T Lee

[link url=""]MIT Technology Review report[/link]
[link url=""]Cell abstract[/link]

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