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Blood infusions from young donors for Alzheimer’s are safe — they may even work

It's not every day that early-stage research at Stanford's School of Medicine generates its own New Yorker cartoon. But a few years ago, news of a discovery by neuroscientist Tony Wyss-Coray, PhD, and his colleagues' -- namely, that blood from young mice can improve older mice's performance on the mouse equivalent of an IQ test -- spawned a pile of press coverage big enough to rate its own zip code.

While the popular imagination was piqued by the thought that, just maybe, Count Dracula had it right, more sober minds reflected on the discovery's potential medical applications. Wyss-Coray, for one, co-founded a biotechnology company called Alkahest, which in turn has funded a clinical trial at Stanford to see if it's even safe, let alone effective, to give young blood to older patients with Alzheimer's disease. This condition, marked by the progressive loss of memory and thinking skills, is an extreme case of what happens to virtually all of us if we live long enough.

In the first part of the trial, led by Stanford clinical neurologist Sharon Sha, MD, some patients with mild to moderate Alzheimer's symptoms got weekly infusions at Stanford of either plasma (the liquid, cell-free portion of blood) from young donors ages 18-20; others got infusions of a placebo (a saline solution). Neither patients, nor caregivers, nor clinicians knew which patient was given which. The investigators scored patients' memory and thinking skills, moods, and caregiver-reported "functional ability": i.e., patients' ease at getting through the day without intensive assistance.

After several weeks, the regimen was reversed: Patients who'd been getting real plasma were switched to placebo, and vice versa.

After nearly six months of patient's and caregivers' shuttling back and forth to Stanford's campus once a week, the clinical researchers adjusted the study design to cut the trial time and travel burden in half. From here on out, new recruits received only plasma, never placebo. The newly enrolled patients nonetheless received the full battery of mood, memory and thinking, and functional-ability tests.

The results are now in and were presented on Saturday by Sha at the 10th annual Clinical Trials on Alzheimer's Disease conference in Boston: The infusions are safe and well tolerated by patients. That's good, but it's also expected -- blood plasma infusions are hardly new or exotic. More intriguing was a statistically significant improvement on two measures of caregiver-reported functional ability.

"That was surprising, to me," Sha told me. "The trial wasn't powered to show efficacy."

Could the last batch of caregivers -- specifically the group who knew that patients were getting the real deal -- have been undergoing their own placebo effect, seeing rainbows through their tears?

From my news release about the trial:

[E]xamination of the data indicated that, to the contrary, it was the first group of participants -- who had no idea whether they were getting plasma or placebo -- who showed the most improvement in functional ability after receiving plasma infusions.

So, the infusions are safe. Proving that they're truly effective -- and learning more about the contours of that efficacy -- will require substantially bigger, much more expensive follow-on trials. Meanwhile, Wyss-Coray and his colleagues have been working hard to identify factors in young blood that are responsible, in the hope that a pill can someday substitute for half a pint.

Previously: Stanford scientist ponders her interest in the brain, The rechargeable brain: Blood plasma from young mice improves old mice's memory and learning, Protein in human umbilical-cord blood propels old mice's sputtering memory to new heights and Stanford research showing young blood recharges the brains of old mice among finalists for Science magazine's Breakthough of the Year
Image by Clker-Free-Vector-Images

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