Summary: A small group of people with Alzheimer’s disease who received experimental blood plasma infusions from young donors showed signs of improved daily functioning, according to researchers.
Source: Stanford University School of Medicine
Stanford investigators report that an early-phase clinical trial testing young-donor blood plasma infusions in people with mild to moderate Alzheimer’s disease was safe and showed encouraging signals of improved functional ability.
Results from the PLASMA trial (Plasma for Alzheimer’s Symptom Amelioration) were presented on Nov. 4 at the Clinical Trial on Alzheimer’s Disease conference in Boston by Sharon Sha, MD, clinical associate professor of neurology and neurological sciences at Stanford and the study’s principal investigator.
While the primary finding confirmed safety and tolerability—consistent with the long history of plasma use in other medical settings—the trial also produced unexpected hints that repeated infusions of plasma from young donors may improve patients’ ability to carry out everyday tasks essential for independent living, such as managing finances, preparing meals and remembering to take medications.
The PLASMA study was inspired by basic research led by Tony Wyss-Coray, PhD, professor of neurology and neurological sciences at Stanford, demonstrating that factors in the blood of young animals can rejuvenate brain tissue and improve cognition in aged mice. The trial translated that hypothesis into a human, early-phase feasibility and safety study.
Larger studies needed
Sha cautioned that the trial enrolled only 18 participants and that many assessments relied on caregiver reports, so the findings are preliminary. Larger, randomized trials will be required to determine whether young-donor plasma offers a meaningful clinical benefit for people with Alzheimer’s disease.
The single-center trial took place at Stanford Hospital and was sponsored by the biotechnology company Alkahest, which holds intellectual property related to the treatment approach. Wyss-Coray, who co-founded Alkahest and chairs its scientific advisory board, remains a full-time Stanford researcher and was not involved in this clinical trial.
The trial had two stages. In stage one, nine participants with mild to moderate Alzheimer’s received four weekly intravenous infusions of either young-donor plasma (from donors aged 18–30) or placebo (saline) in a double-blind crossover design. After a six-week washout period, treatment assignments were reversed so each participant served as their own control.
Participants and caregivers completed standardized assessments of mood, cognition and functional ability before and after each four-week infusion period. The full crossover schedule required nearly a dozen round trips to Stanford over roughly six months, which proved burdensome for participants and caregivers. To reduce travel in the second stage, the next nine participants received open-label plasma infusions and completed the same battery of assessments over a shortened 10–12 week period.
Adverse events were minimal. Investigators reported one minor, treatment-related reaction (transient excessive itching), a known potential side effect of any blood-product infusion. One participant experienced a stroke during the washout period after receiving only saline; investigators judged that event unrelated to the study infusions.
Improvements in functional ability
Overall, the pooled analyses detected no significant changes in mood or standard cognitive tests such as list learning and recall—outcomes that often require longer trials to show change. However, on two of three validated measures of functional ability, participants demonstrated statistically significant improvement after receiving young-donor plasma, despite the small sample size.
Sha said the improvement in daily functioning was an unexpected but important finding, especially because it appeared most pronounced in the blinded crossover group rather than the open-label group. That pattern suggests the results were not solely driven by caregiver expectation or placebo effects. Nevertheless, she emphasized caution in interpreting these signals because of the trial’s limited size and early-phase design.
Based on the safety data and the functional-ability signals observed in PLASMA, the sponsor has indicated plans to advance development of a next-generation plasma-derived product intended to treat mild to moderate Alzheimer’s disease. Investigators and sponsors agree that larger, controlled trials are necessary to evaluate efficacy and to better understand potential mechanisms of action.
“These early results are encouraging: repeated infusions of young-donor plasma were well tolerated in older adults with Alzheimer’s disease, and we observed improvements in measures of daily functioning,” Sha said. “However, small trials can produce promising results that do not always replicate in larger studies. Further research is required to determine whether this approach can provide a meaningful clinical benefit.”
Wyss-Coray echoed that cautious optimism: “It is encouraging to see a favorable safety profile and initial signals in human studies, but success in animal models is far easier than demonstrating a true therapeutic effect in people. Larger clinical trials will be needed to confirm these findings.”
Source: Stanford University School of Medicine
Publisher note: Findings were presented at the 10th annual Clinical Trial on Alzheimer’s Disease conference in Boston on November 4, 2017. Image source is listed as public-domain material.
Study context: This was an early-phase safety and feasibility trial (PLASMA) testing repeated infusions of plasma from young donors in people with mild to moderate Alzheimer’s disease; results are preliminary and require confirmation in larger trials.