The young plasma elixir for the elderly?

Vial of plasma – photogram

In the midst of the Covid-19 pandemic, the use of plasma from recovered subjects as a potential therapeutic or preventive resource was looked upon with hope. The technique was soon abandoned due to a lack of significant results. However, the potential of plasma transfusion – the part of the blood that contains proteins and nutrients but not cells – has been studied for decades to achieve regenerative effects. And the recent explosion of these experiments in the United States has led to talk of ‘vampires 2.0’ in search of eternal youth. The origin of blood studies to reverse the biological clock goes back to parabiosis – a technique whereby two organisms (typically, a young and an ‘old’ mouse) are surgically joined together to create a shared circulatory system.

The blood exchange means that some physiological parameters of the less efficient individual can improve thanks to the contribution of molecules contained in the plasma of the other subject. The first documented study related to longevity was done by Frederic Ludwig and Robert Elashoff. More than half a century ago, the two scientists noticed that mice aged 65 years of a human being, when combined with young animals, lived 4/5 months longer than the controls. But interest in parabiosis studies has only recently returned, in particular thanks to Amy Wagers and colleagues at Stanford University, in the laboratory of Irving Weissman and Thomas Rando.

Another line of research is due to the group of Tony Wyss-Coray. Studies in elderly mice showed increased neuronal growth and memory improvements after 10 blood transfusions from young mice. According to the researchers, in addition to oxygen, blood carries important messenger molecules. By studying these communication factors, it has been noted that half of them change with aging. A protein in human umbilical cord blood has therefore been shown to improve memory and learning in older mice, with obvious behavioral effects. Umbilical blood was given to mice that were genetically engineered in order to have an immune system that avoided rejection of human tissues. After being injected every 4 days for 2 weeks, the blood reactivated neurons in the hippocampus of older animals, which improved their performance in classic labyrinth tests. Definitive results are still far away but, as can easily be hypothesized, the idea of ​​extracting plasma from young blood and then infusing it in the elderly has forcefully entered the range of experimental treatments that promise concrete benefits.

With a series of ambitious start-ups aiming to ride this market. One of them, called Ambrosia, has recently attracted a lot of attention. His research did not need US Food and Drug Administration (FDA) approval because transfusions are an established medical procedure. Patients tested included young people determined to stay healthy and older people (with Alzheimer’s and diabetes) who sought improvement in their condition. The blood was purchased, in line with current regulations, from collection centers where young people donate without compensation. And in the United States, doctors can easily purchase plasma, which is considered a prescription drug.

Tests on mice have provided promising results, creating high expectations for the passage to humans. Start-ups are born driven by substantial capital, but in the meantime ethical questions multiply

Despite the announced successes, however, in February 2019, the FDA put Ambrosia under observation for lack of scientific documentation. After a few months of limited activity, the company returned to operations in Florida, and then closed completely last August. Meanwhile, founder Jesse Karmazin has created a new company called Ivy Plasma, which does similar business, but without specifying where the blood comes from. Other realities are on the launch pad or already in action. A start-up called Alkahest was founded by biologist Wyss-Coray and co-funded by a Hong Kong billionaire whose grandfather with Alzheimer’s is expected to benefit from plasma transfusions, and the Plasma Company Grifols, which invested 37.5 million dollars. The trial consists in the transfusion of plasma from 18-30 year old donors to 18 Alzheimer’s patients once a week for 4 weeks: the aim is to evaluate the safety of the procedure and the possibility of improving cognitive deficits. Individuals with mild to moderate Alzheimer’s disease between the ages of 54 and 86 are divided into two ‘blinded’ groups: one received plasma, while the other received saline only. According to preliminary results, there were no adverse reactions and patients reported modest improvements.

On a different front, Wagers embarked on an entrepreneurial path by founding the company Elevian, which now intends to exploit the growth differentiation factor GDF11, which she identified in the plasma of mice with experiments with controversial existences. When directly infused in animal models, it appears to have produced an increase in muscle tone and strength and has been shown to be beneficial for the liver, spinal cord and brain. Now we want to test whether laboratory-synthesized versions of GDF11 can help treat stroke and other age-related diseases in humans. Elevian raised $ 15 million last year to further advance the therapy. It is clear that, if the promises of companies in the ‘rejuvenation’ sector were to be confirmed, even partially, the market potential would be enormous. This means that there is a very high risk of creating illusions and selling ineffective treatments to those who aspire not only to avoid the typical diseases of old age but to counteract the (natural) process of organic senescence.

For some time it has been debated whether aging should be considered a disease to be treated or not, and the potential treatments would also culturally orientate in the direction of pathologizing the elderly. Other controversial bioethical issues could also add up in the plasma market, from the exploitation of donors to the inequalities created by the fact that only a few very wealthy individuals could access expensive treatments. In general, the race to eternal youth of the new ‘vampires’ – obtained medically – could end up distorting relationships and alternating between generations, curbing the healthy turnover in command posts and undermining the entire social structure to as we know it.

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