“Young Blood” Transfusions Are Not Ready For Primetime – Yet
A young woman donates blood.
The world of dementia research erupted into cheers when news of the first real victory in a clinical trial against Alzheimer's Disease in over a decade was revealed last October.
By connecting the circulatory systems of a young and an old mouse, the regenerative potential of the young mouse decreased, and the old mouse became healthier.
Alzheimer's treatments have been famously difficult to develop; 99 percent of the 200-plus such clinical trials since 2000 have utterly failed. Even the few slight successes have failed to produce what is called 'disease modifying' agents that really help people with the disease. This makes the success, by the midsize Spanish pharma company Grifols, worthy of special attention.
However, the specifics of the Grifols treatment, a process called plasmapheresis, are atypical for another reason - they did not give patients a small molecule or an elaborate gene therapy, but rather simply the most common component of normal human blood plasma, a protein called albumin. A large portion of the patients' normal plasma was removed, and then a sterile solution of albumin was infused back into them to keep their overall blood volume relatively constant.
So why does replacing Alzheimer's patients' plasma with albumin seem to help their brains? One theory is that the action is direct. Alzheimer's patients have low levels of serum albumin, which is needed to clear out the plaques of amyloid that slowly build up in the brain. Supplementing those patients with extra albumin boosts their ability to clear the plaques and improves brain health. However, there is also evidence suggesting that the problem may be something present in the plasma of the sick person and pulling their plasma out and replacing it with a filler, like an albumin solution, may be what creates the purported benefit.
This scientific question is the tip of an iceberg that goes far beyond Alzheimer's Disease and albumin, to a debate that has been waged on the pages of scientific journals about the secrets of using young, healthy blood to extend youth and health.
This debate started long before the Grifols data was released, in 2014 when a group of researchers at Stanford found that by connecting the circulatory systems of a young and an old mouse, the regenerative potential of the young mouse decreased, and the old mouse became healthier. There was something either present in young blood that allowed tissues to regenerate, or something present in old blood that prevented regeneration. Whatever the biological reason, the effects in the experiment were extraordinary, providing a startling boost in health in the older mouse.
After the initial findings, multiple research groups got to work trying to identify the "active factor" of regeneration (or the inhibitor of that regeneration). They soon uncovered a variety of compounds such as insulin-like growth factor 1 (IGF1), CCL11, and GDF11, but none seemed to provide all the answers researchers were hoping for, with a number of high-profile retractions based on unsound experimental practices, or inconclusive data.
Years of research later, the simplest conclusion is that the story of plasma regeneration is not simple - there isn't a switch in our blood we can flip to turn back our biological clocks. That said, these hypotheses are far from dead, and many researchers continue to explore the possibility of using the rejuvenating ability of youthful plasma to treat a variety of diseases of aging.
But the bold claims of improved vigor thanks to young blood are so far unsupported by clinical evidence.
The data remain intriguing because of the astounding results from the conjoined circulatory system experiments. The current surge in interest in studying the biology of aging is likely to produce a new crop of interesting results in the next few years. Both CCL11 and GDF11 are being researched as potential drug targets by two startups, Alkahest and Elevian, respectively.
Without clarity on a single active factor driving rejuvenation, it's tempting to try a simpler approach: taking actual blood plasma provided by young people and infusing it into elderly subjects. This is what at least one startup company, Ambrosia, is now offering in five commercial clinics across the U.S. -- for $8,000 a liter.
By using whole plasma, the idea is to sidestep our ignorance, reaping the benefits of young plasma transfusion without knowing exactly what the active factors are that make the treatment work in mice. This space has attracted both established players in the plasmapheresis field – Alkahest and Grifols have teamed up to test fractions of whole plasma in Alzheimer's and Parkinson's – but also direct-to-consumer operations like Ambrosia that just want to offer patients access to treatments without regulatory oversight.
But the bold claims of improved vigor thanks to young blood are so far unsupported by clinical evidence. We simply haven't performed trials to test whether dosing a mostly healthy person with plasma can slow down aging, at least not yet. There is some evidence that plasma replacement works in mice, yes, but those experiments are all done in very different systems than what a human receiving young plasma might experience. To date, I have not seen any plasma transfusion clinic doing young blood plasmapheresis propose a clinical trial that is anything more than a shallow advertisement for their procedures.
The efforts I have seen to perform prophylactic plasmapheresis will fail to impact societal health. Without clearly defined endpoints and proper clinical trials, we won't know whether the procedure really lowers the risk of disease or helps with conditions of aging. So even if their hypothesis is correct, the lack of strong evidence to fall back on means that the procedure will never spread beyond the fringe groups willing to take the risk. If their hypothesis is wrong, then people are paying a huge amount of money for false hope, just as they do, sadly, at the phony stem cell clinics that started popping up all through the 2000s when stem cell hype was at its peak.
Until then, prophylactic plasma transfusions will be the domain of the optimistic and the gullible.
The real progress in the field will be made slowly, using carefully defined products either directly isolated from blood or targeting a bloodborne factor, just as the serious pharma and biotech players are doing already.
The field will progress in stages, first creating and carefully testing treatments for well-defined diseases, and only then will it progress to large-scale clinical trials in relatively healthy people to look for the prevention of disease. Most of us will choose to wait for this second stage of trials before undergoing any new treatments. Until then, prophylactic plasma transfusions will be the domain of the optimistic and the gullible.
Urinary tract infections account for more than 8 million trips to the doctor each year.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
A surgeon at Massachusetts General Hospital prepares a pig organ for transplant.
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.