Researchers have used an ultrasound implant to open up the blood-brain barrier of patients with a brain tumour. For an hour, this allowed molecules to enter the brain that would normally encounter that barrier. This technique opens the door to new drugs in the fight against brain cancer.
Scientists have successfully developed the blood-brain barrier opened to be able to give new medicines to patients with a brain tumor. This was done with an ultrasound implant. The treatment of brain tumors is still limited because only molecules with certain properties can cross the blood-brain barrier. Medicines that consist of molecules without those properties, such as proteins, cannot enter the brain. The selection of drugs suitable for brain disorders is therefore limited.
Drug Blockade
The blood-brain barrier protects your brain from disease by keeping bacteria and toxins out of your brain. The barrier consists of cells called astrocytes that surround the blood vessels of your brain. Only molecules with certain chemical properties, for example fat-loving molecules, get through without the permission of an astrocyte. This means that hormones can enter your brain freely, for example, and molecules such as insulin must be actively taken in by astrocytes.
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The molecules of many drugs cannot cross the barrier, making brain tumors difficult to treat. Certain types of chemotherapy and drugs made from proteins, such as the recently introduced antibody therapy, do not enter the brain. So doctors need a way to get around that barrier.
Echo waves
The ultrasound implant offers a solution for this. The patient is first injected with microbubbles filled with air into the bloodstream. In the area of the brain that can be reached by the implant’s echo waves, these bubbles begin to vibrate. In doing so, the bubbles ‘pry’ small openings in the blood-brain barrier, as it were, explains blood-brain barrier researcher Olaf van Tellingen from the AMC. That process takes about four minutes. After an hour the barrier is restored.
Seventeen patients with a so-called glioblastoma, a deadly brain tumor, participated in the study. After surgeons surgically removed as much of the tumor as possible, they placed the ultrasound implant in a six-by-six-centimeter skull opening. This opening is necessary because the echo waves cannot pass through the bone.
The patients in the study received ultrasound chemotherapy treatment between two and six times. The concentration of chemotherapy in their brain was six times higher in the part that was opened up by the ultrasound, compared to the rest of the brain. The ultrasound implant was able to open up about 53 milliliters of brain tissue, more than previous techniques but not yet fully sufficient for large tumours.
Exploratory research
An important discovery during this study is the speed with which the blood-brain barrier closes again after an ultrasound treatment. This seems to happen 30 to 60 minutes after activating the ultrasound implant. Previous studies in humans and animals previously found a time frame of 6 to 24 hours. With this more precise knowledge, doctors can better estimate when to give patients their medicines to ensure that as much medication as possible reaches the brain. The doctors also discovered how high the concentration of chemotherapy could become before too many side effects occurred.
This study was a so-called phase I study, to see if and for how long the blood-brain barrier would open and what concentration of medication should be used. A phase II study is now underway. The researchers hope to discover whether this treatment method can give patients a longer life. At this point, a glioblastoma is always fatal. By September 2022, when the researchers had finished collecting data, ten of the seventeen participants in the study had died.
“This is a step in the right direction for the treatment of brain tumors,” says neurologist Pam French of the Erasmus medical center, who was not involved in the study. ‘If we can bypass the blood-brain barrier, it will open the door for a whole new class of drugs to be used against brain tumors. The next step is to investigate which medicines these should be.’