Can Young Blood Really Help Treat Alzheimer's?
Injecting the blood plasma of healthy young people into people with Alzheimer's disease appears to be safe, and the practice may even lead to small improvements in daily functioning in Alzheimer's patients, a new small trial suggests.
But not all experts are lining up behind this technique, and instead argue that the science simply isn't there yet to support it.
It sounds a little (OK, a lot) sci-fi: infusing old people with young blood to reverse the scars of aging and disease. Indeed, the concept is more speculative than most science that makes it to the human-testing phase. No one knows why young blood might help improve a degenerative disease like Alzheimer's, and the vast majority of the research so far has been done in rodents. If it works — and that is far from certain — it's a total mystery as to why.
"It's outside of the box," said Dr. Sharon Sha, a neurologist at Stanford University School of Medicine who led the new trial on the safety of the treatment. The research team is making no grand claims about a cure for dementia, Sha told Live Science, but rather wants to push the research forward in the knowledge that it's safe for humans. [6 Big Mysteries of Alzheimer's Disease]
Blood swap
The results of the new trial, which the researchers presented Nov. 4 at the Clinical Trials on Alzheimer's Disease 10th annual meeting in Boston, focused on people with mild or moderate Alzheimer's disease. In the first portion of the trial, nine patients were given either an infusion of blood plasma (the clear portion of blood that contains clotting factors and immune cells, but no red blood cells) or a placebo weekly for four straight weeks. They then went six weeks without treatment and returned for a final four weeks of getting either the plasma or the placebo — whatever they hadn't received the first time. Neither the researchers nor the patients knew which treatment they were receiving at any given time. The patients took cognitive assessments before and after each portion of the trial. They also took assessments of their daily living abilities, such as the ability to pay bills or balance a checkbook, before and after the treatments.
In the second half of the trial, another nine patients took baseline cognitive and daily functioning assessments, got four weeks of weekly plasma infusions and then took another round of assessments.
The main point of the study, Sha said, was to ensure that the plasma treatments were safe. Plasma is already used for conditions in which the body has lost a lot of blood or needs help with clotting, but it can sometimes trigger itching or immune reactions, Sha said. Another concern was whether the plasma transfusions would raise the patients' blood pressure.
There was no evidence of negative side effects from the treatment, the researchers found. And they found tantalizing hints that it might also be useful: Although the plasma treatments didn't alter the patients' scores on cognitive testing, the patients did show small improvements in their ability to function on a daily basis.
Timing concerns
The study wasn't really designed to look for detailed outcomes, Sha said, so it's not clear why improvements showed up in daily functioning but not thinking abilities. It's possible that the cognitive measurements the team used were too broad, or that the four-week time frame of the study was too short, she said. Or perhaps the treatments simply don't do much for cognitive abilities, or even functional abilities.
"The fact that we found some improvement in functional abilities is exciting and promising, but it doesn't mean that it proves improved functional abilities," Sha said. For that, the researchers need a larger human trial spanning a longer time frame, she said.
But not all researchers think that transfusions of young blood will lead to meaningful medical treatments. The new study proves neither benefit nor safety, said Irina Conboy, a professor of bioengineering at the University of California, Berkeley.
For Conboy, who was not involved in the research, larger human trials are premature. The study conducted by Sha and her colleagues was too short-term to determine either benefit or harm from the transfusions, she said. Moreover, the decision to do transfusions for only four weeks seems arbitrary, Conboy told Live Science, and the patients weren't tracked long enough to see long-term side effects, like the development of autoimmune problems, which can take years. [11 Surprising Facts About the Immune System]
"How do you know that, after five weeks, you would not see improvement or something really bad, like side effects?" Conboy said. "Why did you do four weeks and then you stopped?"
Mystery mechanism
The idea of transfusing new blood into old bodies dates back to the 1950s, when researchers would surgically attach two animals (usually rats) so that they shared a blood flow — a process called parabiosis. This method was often used to study metabolism. More recently, scientists have become interested in using parabiosis to understand and attempt to slow aging. In 2012, for example, University of Cambridge-led research found that linking the blood flow of old mice to young mice led to the formation of new myelin in the central nervous systems of the old mice. Myelin is the fatty sheeting that surrounds nerve cells and enables them to conduct electricity rapidly. Since myelination declines with age and in chronic diseases like multiple sclerosis, the researchers hoped that they could isolate something in young blood that drives remyelination in old brains.
The new Alzheimer's trials came out of research done by Tony Wyss-Coray, a Stanford neuroscientist and the founder of the startup Alkahest, which aims to find the factors in blood that promote tissue regeneration. Alkahest was responsible for the current human trial, in collaboration with Sha's Stanford lab. Earlier this year in the journal Nature, Wyss-Coray and his colleagues reported that giving plasma from human umbilical-cord blood to old mice improved the function of the hippocampus, a brain region involved in memory and spatial reasoning, in the mice. The study also found an increase in a blood factor called tissue inhibitor of metalloproteinases 2 (TIMP2) in the brains of the transfused mice, suggesting a possible culprit for the improvement.
TIMP2 isn't the only possibility, though. Another study by Wyss-Coray's team, this one published in the journal Nature Medicine in 2014, found similar improvements in cognitive function in old mice given blood from young mice that, in part, seemed due to the activation of a protein called Creb, or cyclic AMP response element binding protein. It may be a combination of factors, not just one do-it-all protein, that makes the difference, Sha said. [Extending Life: 7 Ways to Live Past 100]
But Conboy noted that these animal studies used older, but not elderly, mice. Those studies were the equivalent of testing the transfusions on healthy 60-year-old humans without dementia, she said. There are animal models of Alzheimer's disease, including genetically modified mice, but tests using those models haven't been done, Conboy said. Nor have the results from Wyss-Coray's team been replicated by outside research groups.
"Typically, before we start any procedure in clinical trials, we do work with animals that model that particular disease, which was not done in this case," Conboy said. Replications of the mouse work should be the next step, she said, not further human testing. Her research, she added, has found that infusions of young blood are not typically enough to alter the physiology of old bodies. In older cells, multiple proteins and molecules are overproduced, and those need to be regulated downward to see therapeutic benefit, Conboy said. Young blood alone can't overpower these effects of age.
Wyss-Coray and his team, on the other hand, think there is some sort of anti-aging power in the blood of the young. Ultimately, the goal is to find these factors and re-create them as a medication, Sha said. "I think we wouldn't want to rely on the youthful population" to donate blood to the elderly, she said.
"There's hope, and people are working on it," Sha said. "It's not the answer yet."
Original article on Live Science.
