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Drugs that boost our brain’s waste-disposal system so it can better remove proteins associated with Alzheimer’s disease have been identified for the first time. The combination of a therapy that is commonly used as a sedative with a medicine that prevents dangerously low blood pressure seems to safely and effectively remove proteins linked to the disease, which could delay its onset by seven years.

“This is a significant step forward,” says at Harvard University, who wasn’t involved in the research. “It could benefit people with neurodegenerative disease, but even for healthy people, maybe you could use it to maximise the function of the brain.”

Our brain removes metabolic waste via the glymphatic system, a network of channels surrounding the blood vessels that pump waste fluid to the lymphatic system, where it is carried to the blood for disposal.

The glymphatic system is most active during deeper phases of sleep, when slow brain waves help push along waste fluid after it has been released from brain cells. But it becomes impaired with age, and especially .

Researchers have previously found that dexmedetomidine, a drug commonly used as a sedative during medical procedures, boosts these brain waves in mice. It also and in mouse models of Alzheimer’s disease.

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To explore dexmedetomidine’s effects in people, at pharmaceutical company Applied Cognition in Redwood City, California, and his colleagues recruited 19 adults – aged 60, on average – who were deprived of sleep for one night in a lab. The morning after, the participants – who had no chronic medical conditions or brain-specific issues – provided blood samples to act as baseline measurements.

They were then given 4 hours while they received an infusion of dexmedetomidine. They also took a drug called midodrine, which treats low blood pressure, a common side effect of dexmedetomidine. When they woke, the participants provided another blood sample.

A few weeks later, the researchers repeated the experiment, but this time, the participants had a placebo pill and saline infusions. The researchers then compared the two post-nap blood samples, accounting for variations in the two baseline samples.

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This revealed that taking dexmedetomidine and midodrine, which the company collectively calls ACX-02, cleared two amyloid and tau proteins that are particularly prone to misfolding and forming clumps more effectively than the placebo/saline intervention.

The team estimates that if ACX-02’s effect were sustained over several years, it could delay the onset or worsening of Alzheimer’s disease by about seven years, based on levels of misfolded amyloid that are typically seen in people who go on to develop the condition, says Dagum. “That would be a significant, meaningful effect for those at risk,” adds team member at the University of Washington in Seattle.

Gu agrees that the scale of improvement seen with ACX-02 could provide relief from Alzheimer’s for about seven years, but adds that this is just an estimate. We still don’t know whether this treatment actually reduces amyloid and tau clumps in the brain, which are thought by many to be the driving force behind Alzheimer’s symptoms, he says.

at the German Centre for Neurodegenerative Diseases in Bonn says that this estimate assumes that a reduction in blood markers of amyloid are linked to a reduction in amyloid clumps in the brain, which may then lessen Alzheimer’s progression. “Therefore, while the calculation suggests a potentially meaningful effect, it should be viewed as a hypothesis rather than a prediction of clinical benefit,” she says.

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Further analysis revealed that ACX-02 seems to work by boosting the number of slow brain waves during a phase of sleep in which the brain transitions from a light to a deeper stage. It also seems to increase the flow of fluid through the brain, so waste can be more quickly cleared. Finally, it appears to cause blood vessels to dilate and constrict more strongly, which pushes fluid more forcefully along glymphatic channels, says Iliff.

Antibody therapies that remove amyloid clumps, like lecanemab and donanemab, are approved in the US and UK, but their impact on symptoms is limited, and side effects include brain bleeding and swelling. “There’s a huge need for new treatments – we know that the antibodies currently used for Alzheimer’s disease are not really working, and they can cause severe side effects,” says Beschorner.

No severe side effects were observed in Iliff’s trial. Boosting the glymphatic system doesn’t activate the brain’s immune cells in the way that antibody therapies do, which quickly raises the risk of side effects, says Dagum. ACX-02 also clears both amyloid-beta and tau. This may mean that its cognitive benefits are larger, says Dagum, adding that the team plans to verify this in studies involving people with early-stage Alzheimer’s disease.

Gu accepts that previous efforts to clear misfolded amyloid-beta and tau from the brains of people with Alzheimer’s disease have had limited benefits. Nevertheless, he adds that if the new approach is safe and effective, it could have a wide use. “It could benefit people with other brain conditions caused by a build-up of misfolded proteins, such as Parkinson’s,” he says. It might even be possible to develop a pill form of dexmedetomidine to treat attention lapses following sleep deprivation, says Iliff.