Pilot Study: Research Team Used Focused Ultrasound to Open Blood-Brain Barrier in Patient With Malignant Brain Tumor

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A team at Sunnybrook Health Sciences Centre in Toronto has used focused ultrasound to enable temporary and targeted opening of the blood-brain barrier, allowing the more effective delivery of chemotherapy into a patient’s malignant brain tumor.

This is the first known report of the noninvasive opening of the blood-brain barrier in a patient, according to a news release announcing the team’s achievement.

Doxorubicin Infused Into Bloodstream With Microbubbles

The team, led by neurosurgeon Todd Mainprize, MD, FRCSC, and physicist Kullervo Hynynen, MSc, PhD, infused the chemotherapy agent doxorubicin, along with tiny gas-filled bubbles, into the bloodstream of a patient with a brain tumor. They then applied focused ultrasound to areas in the tumor and surrounding brain, causing the bubbles to vibrate, loosening the tight junctions of the cells comprising the blood-brain barrier and allowing high concentrations of chemotherapy to enter the targeted tissues.

“The blood-brain barrier has been a persistent impediment to delivering valuable therapies to treat tumors,” said Dr. Mainprize. “We are encouraged that we were able to open this barrier to deliver chemotherapy directly into the brain, and we look forward to more opportunities to apply this revolutionary approach.”

Pilot Study

This patient treatment is part of a pilot study of up to 10 patients to establish the feasibility, safety, and preliminary efficacy of focused ultrasound to temporarily open the blood-brain barrier to deliver chemotherapy to brain tumors. The Focused Ultrasound Foundation is currently funding this trial through its Cornelia Flagg Keller Memorial Fund for Brain Research.

“Breaching this barrier opens up a new frontier in treating brain disorders,” said Neal Kassell, MD, Chairman of the Focused Ultrasound Foundation. “We are encouraged by the momentum building for the use of focused ultrasound to noninvasively deliver therapies for a number of brain disorders.”

Opening the blood-brain barrier in a localized region to deliver chemotherapy to a tumor is a predicate for utilizing focused ultrasound for the delivery of other drugs, DNA-loaded nanoparticles, viral vectors, and antibodies to the brain to treat a range of neurologic conditions, including various types of brain tumors, Parkinson’s, Alzheimer’s and some psychiatric ­diseases.

While the current trial is a first-in-human achievement, Dr. Hynyen, Senior Scientist at the Sunnybrook Research Institute, has been performing similar preclinical studies for about a decade. His research has shown that the combination of focused ultrasound and microbubbles may not only enable drug delivery, but might also stimulate the brain’s natural responses to fight disease. For example, the temporary opening of the blood-brain barrier appears to facilitate the brain’s clearance of a key pathologic protein related to Alzheimer’s disease and improves cognitive function.

A recent study by PhD student Gerhard Leinenga and Jürgen Götz, PhD, from the Queensland Brain Institute in Australia further corroborated Dr. Hynynen’s research, demonstrating that opening the blood-brain barrier with focused ultrasound reduced brain plaques and improved memory in a mouse model of ­Alzheimer’s disease.1

Based on these two preclinical studies, a pilot clinical trial using focused ultrasound to treat Alzheimer’s disease is being organized. ■


1. Leinenga G, Götz J: Scanning ultrasound removes amyloid-beta and restores memory in an Alzheimer’s disease mouse model. Sci Transl Med 7:278ra33, 2015.