A new study led by Australian researchers is offering further insight into how a novel ultrasound technique could help treat Alzheimer’s disease. The findings describe how focused ultrasound can weaken the blood-brain barrier in brain cells from Alzheimer’s patients, potentially improving the uptake of drugs designed to treat the disease.
“The blood-brain barrier is a semipermeable barrier that lines blood vessels in the brain and importantly protects brain tissue, but that protective function also prevents the uptake of drugs and therapies targeting brain diseases,” explains Anthony White, lead researcher on the project from QIMR Berghofer.
Researchers have been exploring the relationship between Alzheimer’s disease and the blood-brain barrier for several years, with early animal studies revealing focused ultrasound may help the brain clear toxic protein clumps associated with neurodegeneration. This new study offers a highly specific investigation into how these kinds of ultrasound pulses can affect the blood-brain barrier in Alzheimer’s brains.
“Our study is the first to look at how the blood-brain barrier cells from human patients can be disrupted to improve the uptake of Alzheimer’s therapies,” says White, “building on previous studies that have explored if ultrasound could be used to reduce amyloid build up in the brains of mice and other animal models.”
The new research took human induced pluripotent stem cells (iPSCs) from patients with a rare genetic mutation that makes them highly likely to develop Alzheimer’s disease. Those iPSCs were then coaxed into becoming brain endothelial cells, to serve as a model of the blood-brain barrier in a brain susceptible to Alzheimer's.
The subsequent ultrasound treatment involved first injecting lipid microbubbles into the cells. When those microbubbles are then exposed to focused ultrasound they can generate tiny, temporary disruptions to the blood-brain barrier. The researchers could then compare these effects to a control of brain endothelial cells derived from healthy iPSCs.
Interestingly, the researchers found the ultrasound treatment had a greater disruptive effect on the Alzheimer’s brain cells than the healthy brain cells.
“The treatment generated openings in the monolayer of the blood-brain barrier of all patients, but the brain endothelial cells of healthy controls repaired themselves quicker than the Alzheimer’s patient cells,” says Lotta Oikari, first author on the new study. “The blood-brain barrier in Alzheimer’s patients was slower to repair, indicating they would be more receptive to drugs and treatments for longer and that brain ultrasound treatment may have to be adjusted differently depending on the type of disease the patient has.”
Clinical trials are currently underway investigating the safety and efficacy of focused ultrasound techniques treating symptoms of Alzheimer’s disease. And, while this research affirms the potential benefits of this new technique, it does also suggest different kinds of neurodegenerative diseases can result in the ultrasound treatment influencing the blood-brain barrier in highly disease-specific ways.
The new study was published in the journal Stem Cell Reports.
Source: QIMR Berghofer
