Ultrasound Breaches Blood-Brain Barrier, Helping Drugs Fight Tumors

2023-05-02
WEDNESDAY, May 3, 2023 -- Brain cancers are notoriously difficult to treat because most chemotherapy drugs can’t breach the blood-brain barrier, a microscopic layer of cells that protect the brain from toxins.
But researchers now say they can temporarily open that barrier and get more chemo to brain tumors, using an experimental ultrasound device.
The technology led to a four- to sixfold increase in chemo drug concentrations within the brains of patients. The researchers observed this increase with two different powerful chemotherapy drugs, paclitaxel and carboplatin. These drugs aren’t typically used to treat brain tumors because they normally can’t cross the blood-brain barrier.
For this study, doctors surgically removed patients’ glioblastoma — the most common malignant brain tumor in adults — and then implanted a grid of nine ultrasound emitters in their skulls.
Within a few weeks of surgery, patients started chemo treatment to kill any residual cancer cells in their brains.
The experimental emitter grid, designed by French biotech company Carthera, opened the blood-brain barrier at large, critical regions of the brain. This allowed the intravenous chemo drug paclitaxel to seep into the brain.
The ultrasound procedure takes about four minutes and is performed with the patient awake, the researchers reported. Patients go home after a few hours.
The blood-brain barrier quickly reestablishes itself following the procedure, with most of its integrity restored within one hour, the study authors said.
The report was published May 2 in The Lancet Oncology journal.
“There is a critical time window after sonification when the brain is permeable to drugs circulating in the bloodstream,” said lead researcher Dr. Adam Sonabend, an associate professor of neurological surgery at Northwestern University Feinberg School of Medicine, in Chicago.
The doctors escalated the dose of paclitaxel delivered every three weeks, using the ultrasound implant to make sure the chemo got to the brain.
The treatment was safe and well-tolerated, the researchers said. Some patients got up to six chemo treatment cycles for their brain tumors.
The findings of this study have formed the basis for a clinical trial in which patients will receive a combination of paclitaxel and carboplatin to their brains, to see if the treatment prolongs their survival.
Glioblastomas are the fastest-growing brain tumors, and they are nearly always advanced when detected. Five-year survival rates are 22% for people aged 20 to 44, 9% for adults 45 to 54, and 6% for those aged 55 to 64, according to the American Cancer Society.
The researchers said the ultrasound technique could be used to help deliver many different types of medication to the brain.
“While we have focused on brain cancer (for which there are approximately 30,000 gliomas in the U.S.), this opens the door to investigate novel drug-based treatments for millions of patients who suffer from various brain diseases,” Sonabend said in a university news release.
Sources
Northwestern University, news release, May 2, 2023
Posted May 2023
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