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Opening blood vessels in the brain with sound waves in Dutch first

For the first time in the Netherlands, a group of researchers will try to temporarily open the blood-brain barrier. In this way they hope to ensure that medicines reach the brain more easily, in order to better treat brain tumors and other brain disorders. The researchers will do this in an innovative way: using sound waves.

Dr. Dannis van Vuurden is principal investigator and pediatric oncologist at the Princess Máxima Center, specializing in brain stem cancer. He leads the new study, funded for €2.5 million by the Hersenstichting (‘Brain Foundation’). Van Vuurden explains: ‘The blood-brain barrier is the brain’s natural protection mechanism. It shields the brain from harmful substances, but also blocks medicines. So the barrier literally stands in the way of treating brain tumors in children.’

In the new study, the researchers will use Focused-Ultrasound (FUS), a technology that can temporarily open the blood-brain barrier to allow drugs to pass through, without the need for surgery. With this technology, the team aims to investigate existing and new medicines. Their question: does the technology allow drugs to reach the brain better, and does that lead to more effective treatment?

Various brain disorders

The natural defense mechanism of the blood-brain barrier makes the brain largely inaccessible to drugs. As a result, treatments for many different brain disorders are often ineffective. Brain tumors are the deadliest cancer in children. The blood-brain barrier also prevents effective treatment in other diseases, such as Alzheimer's and Parkinson's disease.

The research of the Princess Máxima Center is carried out in close collaboration with UMC Utrecht, Amsterdam UMC, location VUmc and LUMC. By working with experts in various brain disorders in the FUS study, the team hopes to achieve results for as many patient groups as possible.

Van Vuurden: ‘The blood-brain barrier is one of the most important obstacles in the search for effective treatment for brain tumors in children, whom in many cases we cannot yet cure. Breaking that barrier with focused ultrasound could be an important step toward better survival and quality of life for children with a brain tumor.’

Targeted sound vibrations

FUS is an innovative, MRI-driven technology. The blood vessels in the brain are temporarily opened with precisely targeted sound vibrations and microbubbles in the blood. This happens at exactly the right place in the brain, so that the drug can work where it is needed. Surgery to open the skull is not needed. The technique has been shown to be safe in previous research and is currently being investigated in clinical studies in the United States and Canada. The technology is not yet applied in this way anywhere else in Europe.

The team will first study how the FUS treatment works in children and adults with a malignant brain stem tumor and in people with Alzheimer's disease. Ultimately, this technology could also be effective for several other brain disorders.

Huge steps

Merel Heimens Visser, director of the Hersenstichting: ‘Brain researchers have made huge steps in recent years. We can now open the blood-brain barrier very locally and deliver medication in a very targeted manner in one place. By funding this project, we as the Brain Foundation want to make this technology possible in the Netherlands as well.

‘The technology will be used in the treatment of brain tumors and tested for safety in Alzheimer’s disease. But we could apply it to better treat even more brain disorders such as Parkinson's disease and depression.’

Four-year study launched

The study will take around four years. First, the technology will be prepared so that everything works properly. After that, both children and adults with brain stem tumors will be treated with the new technology.

In addition, the team will test if drugs can be safely transferred across the blood-brain barrier, both in the laboratory and in patients with Alzheimer's disease. The researchers will also monitor how the drugs spread through the brain after FUS.

At the same time, the researchers will carry out studies in the lab into the brain’s immune system in brain tumors and Alzheimer’s. In future, it could be possible to activate the immune system with FUS against these diseases. The team will also look at other potentially effective drugs to treat these brain disorders with FUS. These drugs could then be investigated in patients in future follow-up studies.

This research project is made possible in part by several donors: Piet Poortman Fonds, C en W de Boer, Stichting Sterk & Positief, JW Wegener Fonds (being established).