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Ultrasound as a potential tool to prevent and treat Alzheimer's disease

Ultrasound technology has been used in medicine for decades, to image internal organs, reduce inflammation, and promote healing in injured body tissues. More recently, however, science has shown that it can also be used as a treatment strategy for neurodegenerative diseases.

As part of our “Develop” series, framed by the UK DRI's mission to discover the causes of neurodegeneration, develop possible treatments and deliver solutions for healthy ageing, this article dives into the motivations and research of UK DRI Emerging Leader Dr Sophie Morse, to understand how to use ultrasound as a treatment.

Sophie Morse (UK DRI at Imperial) has been working for several years now – first in laboratories run by other scientists and then, from the end of 2022, as leader of her own group – to harness ultrasound technology to provide people affected by neurodegenerative diseases with a safe and non-invasive therapy. There are two directions to her research: one proposes the use of ultrasound to modify the behaviour of cells that have altered functions, and another combining this technology with the injection of microbubbles to open the blood-brain barrier, enabling the delivery of drugs and peripheral immune cells into the brain.

The idea that I might have a technology that could help delay the onset of disease, or even treat people who are already affected, is what gives me the motivation to get this to patients.
Dr Sophie Morse

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.

Inspiring and helping, the driving forces behind her motivation

Sophie came to biomedical research from her interests in mathematics and biology and the desire to help people. This is how she came to study Biomedical Engineering, a subject which allowed her to combine these two subjects and desire to help, not on the front line, but rather behind the scenes.

Her research has focused on dementia in particular because she considers it to be a condition that “takes away from people so much of their quality of life, and not only from the person living it but also everyone around them”.

“The idea that I might have a technology that could help delay the onset of disease, or even treat people who are already affected, is what gives me the motivation to get this to patients, Sophie expresses.

Since the end of 2023, Sophie has been able to develop these lines of research in her own lab, as a UK DRI Emerging Leader, which aims to support research fellows on their path to independence so that they can push their own ideas forward... and those of their students.

“I give my students the freedom to explore their own ideas and like to inspire people to stay in this career rather than abandon it. I have seen many brilliant women leave academia for various reasons, and think it’s a great loss,” she says.

The Emerging Leader programme has increased exposure for Sophie's work, which is key in her pursuit of developing the research she leads. According to her, the research opportunities and the network of contacts she has been able to establish are in part thanks to this initiative, which helped her career take an important leap forward.

“It's a valuable springboard to get to the next level,” she concludes.

Find out more about Dr Sophie Morse's research by visiting her UK DRI profile.

Article published: 2 September 2024
Image credits: Pixabay / Loaivat, Imperial College London, Dr Sophie Morse