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Results from the Alkahest Study of Young Plasma Transfusion

Alkahest is one of the groups trying transfusion of young blood plasma into old individuals as a way to reduce specific measures of aging, an outgrowth of parabiosis studies in which the circulatory systems of young and old animals are linked. The evidence for benefits to result from signals present in young blood is decidedly mixed, with the most compelling studies suggesting that it is a dilution of harmful signals in old blood that lies at the root of changes. Nonetheless, human studies of periodic transfusions of young blood plasma are proceeding. This small pilot study is really only assessing safety, and isn't large enough to prove anything when the outcomes are small, unreliable, or non-existent, as appears to be the case, but the company plans to move on to a larger study.

In the context of the view of aging as accumulated cell and tissue damage, changes in the signaling environment of tissues and bloodstream are reactions to that damage. Thus the scope of possible benefits is not large: the damage remains even if an approach could somehow adjust all relevant signal molecule levels to be exactly the same as they are in young individuals, and that damage is the primary issue. The past few decades of stem cell therapies, which largely work by changing the signaling environment, are pointers to the expected scope of benefits in the best case. Clearly there are some gains to be found in this strategy, but they are ultimately limited by the underlying cell and tissue damage that is the root cause of aging. It must be repaired to truly attain rejuvenation, and if the damage is repaired then the changes in the signaling environment will revert themselves.

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. Caregivers for 16 people with mild or moderate Alzheimer's disease reported that their charges performed slightly better at daily tasks after receiving weekly injections of young plasma. 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 - is "encouraged" to run more trials

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. Two patients dropped out of the trial, one after developing a rash from an infusion and another who had an unrelated stroke.

After receiving young plasma, the 16 remaining patients performed no better 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' scores also improved modestly on another survey that asks caregivers how well patients can perform simple tasks like getting dressed and shopping. The positive effects reported by the caregivers could merely be a placebo effect: "Patients could feel better because somebody paid attention to them."

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. Alkahest also wants to test a range of doses and include patients with more severe Alzheimer's.

Link: http://www.sciencemag.org/news/2017/11/blood-young-people-does-little-reverse-alzheimer-s-first-test

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