Focused Ultrasound Can Be Used To Deliver Drugs to Surgically Inaccessible Brain Lesions

Cerebral cavernous malformations (CCMs), commonly known as cavernomas, are clusters of abnormally grown capillaries in the brain or spinal cord. These growths can lead to serious health issues including seizures, severe headaches, paralysis, and potentially fatal bleeding in the brain. Surgical removal is often the primary treatment for symptomatic cavernomas. A team of researchers is now developing an innovative method for drug delivery to these lesions, employing a combination of focused ultrasound and microbubbles. This technique aims to penetrate the brain’s protective blood-brain barrier, which usually prevents drugs from reaching the malformations.

CCMs are estimated to exist in one out of every 500 individuals. While many of these lesions remain asymptomatic, they can cause significant health problems for some, with symptoms escalating as the blood vessels grow. Surgical removal of these malformations can be hazardous, and medication often fails to reach the target due to the blood-brain barrier. This barrier is crucial for protecting the brain from harmful substances, but it also restricts access to many therapeutic treatments, particularly larger biologic drugs. The research team at UVA Health (Charlottesville, VA, USA) is focusing on temporarily disrupting this barrier in a highly targeted manner. Their method involves the use of microbubbles combined with focused ultrasound waves to momentarily open the blood-brain barrier at specific locations. This temporary opening permits drug penetration to areas that are typically inaccessible.

Impressively, their experiments in a genetically accurate mouse model of the disease revealed that the combination of sound waves and microbubbles alone could stabilize CCMs, even without additional medication. This discovery implies potential additional benefits of this method, extending beyond just facilitating drug delivery. Currently, the researchers are perfecting an image-guided system that allows doctors to observe the opening of the blood-brain barrier in real-time, ensuring precise drug delivery. Their next steps involve understanding how to best use these drugs to control and possibly reduce the size of the cavernomas. Their ultimate goal is to manage the growth of these lesions non-invasively, eliminating the need for invasive skull surgery. If successful, this could revolutionize the treatment and management of CCMs.

“Many CCM patients are in desperate need of more effective treatment options. Some patients have surgically inaccessible lesions that can only be treated with radiation, but such treatments can have strong side effects and take a long time to show efficacy,” said Richard J. Price, Ph.D., who is leading the research team. “We ultimately wish to treat these lesions non-invasively with biologic drugs and gene therapies, but these therapies are relatively large in size and do not penetrate well into brain tissue. Low-intensity focused ultrasound can be steered almost anywhere in the brain. It gives us a unique opportunity to precisely deliver such advanced therapies right to the CCM.”

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