Changing cell behaviour using ultrasound
Ultrasound technology can be used to modulate the activity of glial cells, which are essential cells for brain functioning.
“Ultrasound is a pressure wave which can influence the mechanically sensitive ion channels in the cell membrane. This can change the behaviour of cells,” Sophie says.
In the case of, for example, microglia – the brain’s resident immune cells that clear away debris and dead cells – the technique can increase the amount of clearance that these cells carry out in the brain. This could be particularly useful at certain stages of Alzheimer's, when microglia’s ability to clear unwanted compounds become dysfunctional. Even at more advanced stages, when inflammation builds up in the brain, ultrasound could influence these cells and decrease inflammation.
“It is a way of controlling from the outside of the brain cellular behaviour that is dysfunctional and is creating a problem in the brain,” summarises the researcher.
In this research, Sophie's group are trying to establish the limits of the technology. They are undertaking in vitro and in vivo tests to understand which behaviours can be modulated and the mechanism, to improve the types of treatments it can deliver. The idea is that in the future – after understanding what they can achieve and what is most useful at different stages of the disease – the scientists can develop a device or apply an existing one to deliver the treatment to patients.
Opening barriers
The other line of research that Sophie’s team is focused on involves the ultrasound technology as well but aimed at the blood-brain barrier.
This barrier is a network of blood vessels and tissue made up of closely packed cells. While its purpose is to protect the brain and prevent harmful molecules and substances from entering, that very function also blocks drugs from reaching the brain.
For a couple of decades, researchers have been working on a technique that involves using ultrasound technology and injecting microbubbles into the bloodstream to temporarily open the barrier, and allow the passage of drugs needed by the patient into the brain. Sophie's research has focused on advancing this development by making it as safe as possible.
The technique involves focusing ultrasound from outside the human body into target brain regions and injecting the microbubbles and the preferred drug into the bloodstream.
The ultrasonic pressure waves drive the microbubbles to oscillate as they expand and contract, which creates mechanical pressure on the walls of the blood vessel.
“It is a mechanical action that does several things. On one hand, it opens up the junctions in between the cells that form the blood vessels so that drugs can go through. And on the other hand, it increases the number of drug molecules that can go through the cells and the ones that do get across are less likely to be pumped straight back out into the bloodstream,” explains the UK DRI researcher.
Currently, this line of research is at a “very exciting” stage, according to Sophie, as clinical trials are underway in different parts of the world, including Canada, the US, Taiwan, and France, and she is confident that the UK will join very soon.
“These countries are going through clinical trials and are showing that the treatment is safe. They are now testing out different types of drugs to see how much of an effect it has and how it can be taken to the next level, so that it can be approved,” she comments.
