Researching "Young Blood" and Alzheimer's

"We thought it would be safe and it is. What's really exciting is that in such a short period of time we found an improvement in functional ability."
"Anecdotally, caregivers would tell me that their patients were more engaged, more involved in conversations and paid attention more."
"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."
"Dr. Sharon Sha, clinical associate professor of neurology, Stanford University

"I think there was really zero experimental evidence before clinical trials that it might work."
"Alzheimer's disease doesn't come from just getting old. There is an accumulation of toxic plaques in the brain and it's almost impossible to get rid of them."
Dr. Irina Conboy, leader in 'parabiosis', University of California, Berkeley

A company is testing whether plasma from young donors can help patients with Alzheimer’s disease.

Christian Charisius/picture-alliance/dpa/AP Images

Stanford University neuroscientist Tony Wyss-Coray published a study in Nature in 2014 in which he and his research team conjoined a young mouse with an old one surgically to resemble Siamese twins. Exposed to the blood plasma of the young mice, the old mice outperformed other laboratory old test mice that had been transfused with blood plasma from old rodents whereas the old mouse brains exposed to young plasma acquired more new neurons, less inflammation and more synapses/connections between neurons.

It was this very trial and the published study that came out of it that provided the rationale and the impetus for a new trial led by Dr. Sha of Stanford University, representing the world's first study to test whether infusing the liquid portion of blood into elderly people with Alzheimer's disease might be beneficial. The treatment resulted in "hints" that improved ability to perform basic tasks like making breakfast or paying bills could be possible when these patients were infused with youthful plasma.

Still, Dr. Wyss-Coray, observing the study results in publication form was none too enthusiastic about the results, stating that it has been his experience that it is relatively simple to cure disease in small animals "and a million times more difficult in humans". As for Dr. Conboy and her experiments, she pointed out that earlier mouse experiments that represented human umbilical cord blood involving old mice she had undertaken used old mice, and not genetically modified mice mimicking Alzheimer's.

Her parabiosis experiments concluded that when young mice and old mice exchange blood, young mice become "dumber" and stop developing new neurons in the brain. Parabiosis is a technique, now a century old, involving experimentally uniting the circulation systems of two animals. The new study where Stanford researchers were involved in injections of a protein found liberally in human umbilical cord blood had the effect of revitalizing aged mice's hippocampus resulting in their old brains appearing to behave younger.

Results from the world’s first study to test infusing youthful plasma — the pale yellow 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. Getty Images

Nine senior patients diagnosed with mild to moderate Alzheimer's were infused four times weekly with plasma from male donors between the ages of 18 to 30, and alternately, with a placebo. A six-week "washout" period followed where the regimens were then reversed so that those patients who had been given plasma received four weekly infusions of a placebo and the placebo patients were infused with plasma. Another group of nine patients received simply plasma, no placebo.

There were no significant alterations on scales measuring mood or cognitive function, according to a final analysis, yet modest improvements based on caregivers' anecdotal reports were recognized in day-to-day activities. It is thought that the study, of six months' duration might have been too short an exposure to produce meaningful changes in cognition, stated Dr. Sha.

The end result for this trial, however, was the agreement that no detectable changes in memory, language, attention or other signs of cognitive function arose following the infusions. Despite which the report's authors feel the results represent a confidence-builder that the time is right to move toward a larger study with greater numbers of people involved. Dr. Sha is the principal investor of the PLASMA (Plasma for Alzheimer's Symptoms Amelioration) trial.

There are  skeptics from within the research community who feel insufficient evidence exists from animal studies to begin injecting young blood into old people on the theory that it might be possible with this technique to reverse Alzheimer's. Dr. Sha's study was paid for by Alkahest, a biotech company co-founded by her Stanford University colleague, neuroscientist Tony Wyss-Coray.

Illustrations of stages of the parabiosis surgery adapted from photographs in Conboy & Conboy Via Aging Cell