The first rigorous clinical test of whether blood plasma donated by healthy young people can help reverse Alzheimer’s disease in older adults has found that the treatment produced minimal, if any, benefits.
In the study of 18 people with mild or moderate Alzheimer’s disease, caregivers reported that on average their charges performed slightly better at daily tasks after receiving weekly injections of young plasma, according to the abstract of a talk to be presented on Saturday at the 10th Clinical Trials on Alzheimer’s Disease meeting in Boston. But the patients did no better on cognitive tests administered by researchers—a crucial standard for whether the treatment had a significant impact. All the same, the sponsor of the trial—startup company Alkahest in San Carlos, California, is “encouraged” to run more trials, says CEO Karoly Nikolich.
The notion that young blood may have antiaging or other beneficial properties comes from 150-year-old experiments that stitched together the skins of two still-living old and young mice, allowing their circulation to be shared. Researchers who recently revived the technique have reported that this so-called parabiosis revitalizes the liver, muscles, and brain of the old mice. They are now hunting for molecules within young blood that may explain these apparent antiaging effects.
Three years ago, neuroscientist Tony Wyss-Coray’s lab at Stanford University in Palo Alto, California, found that injections of the plasma portion of blood from young mice could achieve the same antiaging effects as parabiosis in old mice. And his group reported last year that injections of young mouse plasma improved cognitive function in mice with a form of Alzheimer’s.
To test whether young plasma could similarly help people with Alzheimer’s, Alkahest—which Wyss-Coray co-founded—sponsored a small trial led by Stanford neurologist Sharon Sha. Nine patients with mild to moderate Alzheimer’s got four once-weekly infusions of either saline (as a placebo) or plasma from 18- to 30-year-old male donors. After a 6-week break, the infusions were switched so that the patients who had gotten plasma got saline, and the patients who had gotten saline received plasma. Another nine patients received young plasma only, and no placebo. Several patients dropped out of the trial for various reasons, including one who developed a rash from an infusion and another who had an unrelated stroke.
The remaining patients who completed the young plasma treatment performed no better overall on objective cognitive tests given by medical staff. However, on average their scores improved slightly—4.5 points on a 30-point scale—on a caregiver survey about whether they needed help with daily activities such as making a meal or traveling. The patients’ average scores also improved modestly on another survey that asks caregivers how well patients can perform simple tasks like getting dressed and shopping.
Non–Alkahast affiliated Alzheimer’s researchers who have read the abstract are intrigued but cautious. Howard Feldman of the University of California, San Diego, calls the results “interesting,” but adds that the study raises many questions, such as what cellular process in the brain the treatment is targeting.
That’s what neuroscientist Zaven Khachaturian, who retired from the National Institute on Aging in Bethesda, Maryland, and is now a scientific advisor to the Alzheimer’s Association, wants to know. “They need to explain the potential mode of action,” he says. He wants to keep an “open mind,” but adds that the positive effects reported by the caregivers could merely be a placebo effect: “[Patients] could feel better because somebody paid attention to them.”
Wyss-Coray agrees that not much can be concluded from the small trial, but says, “It’s tempting to feel hopeful about the improvement in functional scores.” Because the treatment seemed safe, Alkahest now wants to launch another trial that will use just the fraction of the blood plasma that contains growth factors, but not coagulation factors and other components that may do more harm than good. In animals, this plasma fraction was more effective at improving cognition in the mice with an Alzheimer’s-like condition than whole plasma, Wyss-Coray says. Alkahest also wants to test a range of doses and include patients with more severe Alzheimer’s.
Resolving whether young plasma works has recently taken on an increased urgency, as a private clinic in California is already offering plasma infusions for people, sick or healthy, willing to pay $8000 for a 2-day young plasma treatment. That treatment has been characterized by the company as a “clinical trial,” but researchers have criticized the effort as unscientific.
*Correction, 8 November, 10:35 a.m.: The number of patients who completed the study has been corrected.