An experimental treatment approach for Alzheimer’s disease that uses microscopic gas bubbles excited by ultrasound energy to temporarily breach the blood-brain barrier and break up amyloid plaques is set to be tested in humans for the first time. According to a press release by the Queensland Brain Institute (QBI), a $10 million (ASD) government grant combined with public donations has provided nearly all the funding needed for a phase 1 trial. They anticipate to enroll and begin treating a small group of patients late next year. 

Earlier this year, a University of Queensland research team published study results showing that their non-invasive technique successfully reversed dementia symptoms and lowered the number of plaques in elderly mice when combined with an antibody drug agent. Past investigations had demonstrated that the excited microbubbles alone are effective at removing plagues in a rodent model of Alzheimer’s.

"All brains change with age, potentially making them more fragile. As Alzheimer’s is an age-related disease, we wanted to investigate whether our ultrasound technology is safe for use on older brains," investigator Dr Gerhard Leinenga said in a statement in February. "The mice we treated in this study would be the human equivalent of 80 to 90 years old. With age, they are known to have cerebral amyloid angiopathy (CAA) – the build-up of toxic amyloid in blood vessels.”

“The technology temporarily opens the blood-brain-barrier to remove toxic plaques from the brain and has successfully reversed Alzheimer’s symptoms and restored memory function in animal models,” QBI Director Professor Pankaj Sah said in today’s statement.

The blood-brain barrier (BBB) is a highly selective shielding, made of specialized flattened cells, that wraps around all the blood vessels in the central nervous system. It serves to protect neural tissue from pathogens and toxins circulating in the bloodstream while letting in respiratory gases, sugars, and small signaling molecules like hormones. And though the BBB does a good job at preventing dangerous elements from entering the brain, it also blocks the entry of most drugs and limits movement and activation of immune cells.

As a consequence, the body is incapable of clearing amyloid-β and tau protein accumulations on its own (we still don’t fully understand why they form in the first place) and creating treatments that can do the job effectively has been very challenging.

There are currently no approved therapies for Alzheimer’s or any other type of dementia, only drugs that help manage side effects.

The QBI team’s approach to combatting dementia is ingeniously simple. Excited by the ultrasound energy, the microbubbles pulsate within brain blood vessels, which pushes the cells that form the BBB apart. When there are gaps in the barrier, the drug molecules and natural immune system-boosting molecules that are normally excluded from the brain can rush in to combat the plaques.

As promising as the animal study results may be, other researchers have recently suggested that the so-called "amyloid hypothesis" of dementia could be incorrect or incomplete. After a string of drugs designed to either eliminate these proteins or stop them from forming totally failed in clinical trials, many began to question the long-standing notion that plaques are the underlying cause of dementia symptoms.

In their past studies, the QBI team observed that reduction in plaques by microbubbles with and without antibodies was accompanied by a reduction in symptoms, suggesting a cause and effect relationship, but it is possible that the transient opening of the BBB induced other brain changes that were ultimately responsible for improving the mice’s neurological health.

One thing that we do know for certain? Results from the upcoming phase 1 trial will be eagerly awaited.