Novel ultrasound device temporarily opens blood-brain barrier to deliver chemotherapy
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For the first time, a novel ultrasound implantable device has temporarily opened the blood-brain barrier to deliver cancer drugs. This significant milestone is critical for treating glioblastoma, a deadly brain tumor.
The blood-brain barrier is a microscopic structure formed by closely packed blood vessels and tissue that keeps harmful substances or drugs away from the brain. As the drugs can’t cross the blood-brain barrier, it also limits the treatment of other brain-related diseases.
Northwestern University researchers conducted the human research trials of this new device. “This is potentially a huge advance for glioblastoma patients. While we have focused on brain cancer, this opens the door to investigate novel drug-based treatments for millions of patients who suffer from various brain diseases,” said Dr. Adam Sonabend, lead investigator of this new device, in an official release.
The development
The blood-brain barrier made it difficult for potent chemotherapy to reach the target tumor. Additionally, it was one of the major obstacles to developing effective and targeted brain tumor treatment.
The first-ever human clinical trial to test the efficacy of this ultrasound method was conducted in this study. The team used a skull-implantable ultrasound device to open the blood-brain barrier temporarily. This enabled chemotherapy to be administered intravenously to the human brain. Paclitaxel and carboplatin were given to the patients as chemotherapy drugs.
According to the official statement, this procedure to open the blood-brain barrier takes only four minutes and is performed while the patient is awake. The patients were allowed to go home after this treatment within a few hours. For months, this treatment was repeated every few weeks.
“This is the first study to successfully quantify the effect of ultrasound-based blood-brain barrier opening on the concentrations of chemotherapy in the human brain. Opening the blood-brain barrier led to an approximately four- to six-fold increase in drug concentrations in the human brain, the results showed,” noted the official statement.
The barrier recloses quickly
Furthermore, this new study demonstrates that the blood-brain barrier only opens for a brief period of time. Some previous studies claimed that the barrier is restored 24 hours after brain sonication, while others claimed it takes six hours.
The researchers found that blood-brain barrier restoration begins within the first 30 to 60 minutes after the sonication — a method of moving particles that uses sound waves.
“The findings will allow optimization of the sequence of drug delivery and ultrasound activation to maximize the drug penetration into the human brain,” said the statement.
They report that using a novel skull-implantable grid of nine ultrasound emitters developed by the company Carthera, they could open the blood-brain barrier in a volume of the brain nine times larger than the initial device (with a small single-ultrasound emitter). This device is especially effective at directing drugs to a large portion of the tumor.
The study's findings are based on the ongoing phase 2 clinical trial conducted on patients with recurrent glioblastoma. Participants in the study received paclitaxel and carboplatin chemotherapy delivered to the brain via ultrasound. The trial's goal is to see if this treatment improves patient survival.
The research has been published in the journal The Lancet Oncology.
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