Australian researchers are studying if ultrasound therapy can help weaken the blood-brain barrier in Alzheimer’s patients to test whether it would improve the intake of drugs.
Anthony White, lead researcher of the study from QIMR Berghofer Medical Research Institute in Brisbane, Australia explains the blood-brain barrier (BBB):
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.
The BBB, also called the neurovascular unit, is critical in preventing toxic molecules from entering our cells and facilitating the uptake of nutrients. This unit is formed by “brain endothelial cells (BECs), pericytes, astrocytes, and neurons, with BEC-expressed tight junctions inhibiting the entry of unwanted molecules into the central nervous system,” states the research.
Several neurological diseases have been linked to having an abnormal BBB. The research points out it’s important to specifically study Alzheimer’s disease and human BBB testing in order to understand it’s contribution to Alzheimer’s disease pathogens and drug delivery, as White explains:
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. 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.
Induced pluripotent stem cells (iPSCs) are derived from blood or skin cells that were reprogrammed into an ’embryonic-like pluripotent state’. This enables the development of an unlimited source of human cells, which can then be used for therapeutic purposes.
For their research, published in Cell, scientists used human iPSCs from people who have a rare genetic mutation that makes them highly susceptible to develop Alzheimer’s. Then, the team developed the iPSCs into brain endothelial cells as a model of the BBB for the study.
Before doing the ultrasound treatment, they injected lipid microbubbles into the cells. These microbubbles cause very small temporary disruptions to the BBB when they are exposed to ultrasound. The researchers were then able to compare these disruptions from the healthy iPSC cells to those found in Alzheimer’s patients.
Their tests revealed that the ultrasound had a greater disruptive effect on the Alzheimer’s brain cells. Lotta Oikari first author of the study, explains the findings:
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. 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.
Now the team is conducting clinical trials with Alzheimer’s patients to determine how safe the ultrasound treatments are. If they deem this clear this as a safe effective treatment, it will not only be good news for Alzheimer’s patients but for other neurological disorders as well.
There are currently other ultrasound clinical trials happening in the U.S. as well, using low-intensity focused ultrasound pulsation (LIFUP).
