In a potentially game-changing breakthrough for brain cancer patients, researchers have managed to temporarily breach the blood-brain barrier using ultrasound and successfully deliver chemotherapy drugs to the brain.
A new study reports the results of a phase 1 clinical trial, providing the first direct evidence that ultrasound-based opening of the blood-brain barrier can significantly increase concentrations of chemotherapy drugs in the brain.
Using low-intensity sound waves and tiny injectable bubbles, the team was able to deliver the drugs to the brains of recurrent glioblastoma patients, storming the blood-brain barrier in the process. Sneaking past the brain’s most fortified defense is no mean feat, and as such it has beleaguered scientists for decades.
The blood-brain barrier is, as you might have guessed, a barrier between the blood and the brain. This practically impenetrable lining of blood vessels prevents toxins and pathogens from seeping into the central nervous system – but it also acts as a barricade to many medications, making some brain diseases, including cancer, incredibly difficult to treat.
Glioblastoma is one such disease. A common and aggressive brain tumor, it often returns after surgery and currently has no effective treatment.
In an effort to change that, research has turned to ultrasound to break through the blood-brain barrier. Back in 2014, scientists managed to achieve this in the human brain, and since then, the technique has been trialed in the treatment of brain tumors. Until now, however, its efficacy has not been quantified.
"This is potentially a huge advance for glioblastoma patients," neurosurgeon Adam Sonabend from Northwestern University said of the latest findings in a statement.
In a trial involving 17 recurrent glioblastoma patients, Sonabend and colleagues demonstrated that the treatment increased the concentration of chemotherapy drugs in the brain by four to six times what could be achieved normally.
Patients had all previously undergone surgery to remove their tumors, during which a novel ultrasound device was implanted into their brains. Every three weeks, for between two and six cycles of treatment, the devices released a low-intensity pulse of ultrasound. At the same time, patients were injected intravenously with microbubbles, followed by an infusion of a chemotherapy drug: paclitaxel or carboplatin.
When the bubbles encounter a wave of ultrasound, they vibrate, pushing apart the cells of the blood-brain barrier, and allowing the drugs to squeeze through. Within an hour, the trial found, the barrier is fully closed again.
Overall, the treatment was well tolerated, although some side effects were reported, including headaches and hypertension.
Nevertheless, the results are extremely promising and a phase 2 trial is currently underway investigating whether the treatment prolongs survival in glioblastoma patients.
"While we have focused on brain cancer (for which there are approximately 30,000 gliomas in the US), this opens the door to investigate novel drug-based treatments for millions of patients who suffer from various brain diseases," added Sonabend.
The study is published in The Lancet Oncology.