“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.
How sharing, hearing, and remembering positive stories can help shape our brains for the better
Across cultures and through millennia, human beings have always told stories. Whether it’s a group of boy scouts around a campfire sharing ghost stories or the paleolithic Cro-Magnons etching pictures of bison on cave walls, researchers believe that storytelling has been universal to human beings since the development of language.
But storytelling was more than just a way for our ancestors to pass the time. Researchers believe that storytelling served an important evolutionary purpose, helping humans learn empathy, share important information (such as where predators were or what berries were safe to eat), as well as strengthen social bonds. Quite literally, storytelling has made it possible for the human race to survive.
Today, neuroscientists are discovering that storytelling is just as important now as it was millions of years ago. Particularly in sharing positive stories, humans can more easily form relational bonds, develop a more flexible perspective, and actually grow new brain circuitry that helps us survive. Here’s how.
How sharing stories positively impacts the brain
When human beings share stories, it increases the levels of certain neurochemicals in the brain, neuroscientists have found. In a 2021 study published in Proceedings of the National Academy of Sciences (PNAS), Swedish researchers found that simply hearing a story could make hospitalized children feel better, compared to other hospitalized children who played a riddle game for the same amount of time. In their research, children in the intensive care unit who heard stories for just 30 minutes had higher levels of oxytocin, a hormone that promotes positive feelings and is linked to relaxation, trust, social connectedness, and overall psychological stability. Furthermore, the same children showed lower levels of cortisol, a hormone associated with stress. Afterward, the group of children who heard stories tended to describe their hospital experiences more positively, and even reported lower levels of pain.
Annie Brewster, MD, knows the positive effect of storytelling from personal experience. An assistant professor at Harvard Medical School and the author of The Healing Power of Storytelling: Using Personal Narrative to Navigate Illness, Trauma, and Loss, Brewster started sharing her personal experience with chronic illness after being diagnosed with multiple sclerosis in 2001. In doing so, Brewster says it has enabled her to accept her diagnosis and integrate it into her identity. Brewster believes so much in the power of hearing and sharing stories that in 2013 she founded Health Story Collaborative, a forum for others to share their mental and physical health challenges.“I wanted to hear stories of people who had found ways to move forward in positive ways, in spite of health challenges,” Brewster said. In doing so, Brewster believes people with chronic conditions can “move closer to self-acceptance and self-love.”
While hearing and sharing positive stories has been shown to increase oxytocin and other “feel good” chemicals, simply remembering a positive story has an effect on our brains as well. Mark Hoelterhoff, PhD, a lecturer in clinical psychology at the University of Edinburgh, recalling and “savoring” a positive story, thought, or feedback “begins to create new brain circuitry—a new neural network that’s geared toward looking for the positive,” he says. Over time, other research shows, savoring positive stories or thoughts can literally change the shape of your brain, hard-wiring someone to see things in a more positive light.How stories can change your behavior
In 2009, Paul Zak, PhD, a neuroscientist and professor at Claremont Graduate University, set out to measure how storytelling can actually change human behavior for the better. In his study, Zak wanted to measure the behavioral effects of oxytocin, and did this by showing test subjects two short video clips designed to elicit an emotional response.
In the first video they showed the study participants, a father spoke to the camera about his two-year-old son, Ben, who had been diagnosed with terminal brain cancer. The father told the audience that he struggled to connect with and enjoy Ben, as Ben had only a few months left to live. In the end, the father finds the strength to stay emotionally connected to his son until he dies.
The second video clip, however, was much less emotional. In that clip, the same father and son are shown spending the day at the zoo. Ben is only suggested to have cancer (he is bald from chemotherapy and referred to as a ‘miracle’, but the cancer isn’t mentioned directly). The second story lacked the dramatic narrative arc of the first video.
Zak’s team took blood before and after the participants watched one of the two videos and found that the first story increased the viewers’ cortisol and oxytocin, suggesting that they felt distress over the boy’s diagnosis and empathy toward the boy and his father. The second narrative, however, didn’t increase oxytocin or cortisol at all.
But Zak took the experiment a step further. After the movie clips, his team gave the study participants a chance to share money with a stranger in the lab. The participants who had an increase in cortisol and oxytocin were more likely to donate money generously. The participants who had increased cortisol and oxytocin were also more likely to donate money to a charity that works with children who are ill. Zak also found that the amount of oxytocin that was released was correlated with how much money people felt comfortable giving—in other words, the more oxytocin that was released, the more generous they felt, and the more money they donated.
How storytelling strengthens our bond with others
Sharing, hearing, and remembering stories can be a powerful tool for social change–not only in the way it changes our brain and our behavior, but also because it can positively affect our relationships with other people
Emotional stimulation from telling stories, writes Zak, is the foundation for empathy, and empathy strengthens our relationships with other people. “By knowing someone’s story—where they come from, what they do, and who you might know in common—relationships with strangers are formed.”
But why are these relationships important for humanity? Because human beings can use storytelling to build empathy and form relationships, it enables them to “engage in the kinds of large-scale cooperation that builds massive bridges and sends humans into space,” says Zak.
Storytelling, Zak found, and the oxytocin release that follows, also makes people more sensitive to social cues. This sensitivity not only motivates us to form relationships, but also to engage with other people and offer help, particularly if the other person seems to need help.
But as Zak found in his experiments, the type of storytelling matters when it comes to affecting relationships. Where Zak found that storytelling with a dramatic arc helps release oxytocin and cortisol, enabling people to feel more empathic and generous, other researchers have found that sharing happy stories allows for greater closeness between individuals and speakers. A group of Chinese researchers found that, compared to emotionally-neutral stories, happy stories were more “emotionally contagious.” Test subjects who heard happy stories had greater activation in certain areas of their brains, experienced more significant, positive changes in their mood, and felt a greater sense of closeness between themselves and the speaker.
“This finding suggests that when individuals are happy, they become less self-focused and then feel more intimate with others,” the authors of the study wrote. “Therefore, sharing happiness could strengthen interpersonal bonding.” The researchers went on to say that this could lead to developing better social networks, receiving more social support, and leading more successful social lives.
Since the start of the COVID pandemic, social isolation, loneliness, and resulting mental health issues have only gotten worse. In light of this, it’s safe to say that hearing, sharing, and remembering stories isn’t just something we can do for entertainment. Storytelling has always been central to the human experience, and now more than ever it’s become something crucial for our survival.
Want to know how you can reap the benefits of hearing happy stories? Keep an eye out for Upworthy’s first book, GOOD PEOPLE: Stories from the Best of Humanity, published by National Geographic/Disney, available on September 3, 2024. GOOD PEOPLE is a much-needed trove of life-affirming stories told straight from the heart. Handpicked from Upworthy’s community, these 101 stories speak to the breadth, depth, and beauty of the human experience, reminding us we have a lot more in common than we realize.
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
MRI scans after a new kind of immunotherapy for brain cancer show remarkable progress in one patient just days after the first treatment.
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”