Could young blood improve Alzheimer’s?
‘Hints’ young plasma revives old brains
When scientists reported this spring that blood from human babies had made old mice smarter, the next logical step, they said, was to see whether young blood could have the same rejuvenating effects on human brains.
The answer is: maybe, maybe not.
Results from the world’s first study to test infusing youthful plasma — the liquid portion of blood — into elderly people with Alzheimer’s disease found “hints” the controversial treatment improved their ability to perform basic tasks such as making breakfast or paying bills.
However, there were no detectable changes in memory, language, attention or other signs of cognitive functioning after the infusions.
Nevertheless, the authors say the results have given them the confidence to move into a bigger study involving more people.
“We thought it would be safe and it is,” said Dr. Sharon Sha, a clinical associate professor of neurology at Stanford University and principal investor of the PLASMA (Plasma for Alzheimer’s Symptoms Amelioration) trial.
“What’s really exciting is that in such a short period of time we found an improvement in functional ability.”
Others remain unconvinced and say there was insufficient evidence from animal studies to start injecting young blood into old people in the hope of reversing Alzheimer’s.
“I think there was really zero experimental evidence before clinical trials that it might work,” said the University of California, Berkeley’s Irina Conboy, a leader in the field of “parabiosis” — a century-old technique that involves uniting the circulatory systems of two animals.
The rationale for the new trial emanated from the work of Stanford University neuroscientist Tony Wyss-Coray. In a study published in Nature in 2014, Wyss-Coray and his team surgically conjoined a young mouse with an old one, like Siamese twins. On memory tests, old mice exposed to the blood plasma of the young outperformed old mice that got plasma from old rodents. The old mouse brains exposed to young plasma had more new neurons, less inflammation and more synapses or connections between neurons.
Then, in April, Stanford researchers reported that injections of a protein abundant in human umbilical cord blood revitalized the hippocampus in aged mice. Their old brains seemed to act younger.
In the new study, paid for by Alkahest, a biotech company co-founded by WyssCoray, nine seniors with mild to moderate Alzheimer’s were given four weekly infusions of plasma from male donors aged 18-30, or a placebo.
After a six-week “washout” period, the regimens were reversed: those who had received plasma got four weekly infusions of a placebo, and vice versa.
A second group of nine people all received just plasma, and no placebo.
In the final analysis, there were no significant changes on scales measuring mood or cognitive function, but a modest improvement, based on reports from caregivers, on day-to-day activities.
“Anecdotally, caregivers would tell me that their patients were more engaged, more involved in conversations and paid attention more,” Sha said.
“It’s a small clinical trial, so we have to temper that. We also don’t know, what’s the best dosing or length of time.”
The initial study — six months duration, from the first visit to the last — may have been too short to produce, or tease out any meaningful changes in cognition, she said.
The ultimate goal is to identify what component of young plasma might be benefiting people.
Wyss-Coray, who wasn’t involved in the study, tempered his enthusiasm, noting in a statement that it’s easy to cure disease in small animals, “and a million times more difficult in humans.”
Conboy, of UC Berkeley, said the earlier mouse experiments involving human umbilical cord blood involved old mice — not genetically modified mice mimicking Alzheimer’s.
“Alzheimer’s disease doesn’t come from just getting old,” she said. “There is an accumulation of toxic plaques in the brain and it’s almost impossible to get rid of them.”
Her own parabiosis experiments have found that when young mice and old mice swap blood, young mice get “dumber” and stop making new neurons in the brain.