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The cells lining the brain’s blood vessels are tightly packed together—like a good defensive line, they keep bacteria and other blood-borne intruders from getting through, shielding the brain. But this protective layer, called the blood-brain barrier, also thwarts efforts to deliver drugs like chemotherapy agents to the brain, so scientists have long searched for ways to disrupt it selectively to allow treatments in. A startup company called Perfusion Technology is developing a technique to open this barrier by bathing the brain in ultrasound waves.

Ultrasound has been investigated for a decade as a tool for opening the blood-brain barrier. Most techniques, however, rely on specialized equipment to focus the ultrasound waves to a tiny point. They also require an injection with microbubbles to amplify the effect, and an MRI machine to guide the treatment. Al Kyle, president and CEO of Perfusion Technology, which is based in Andover, Massachusetts, says that the company’s method is simpler and cheaper. Rather than opening the blood-brain barrier briefly at a single point, Perfusion uses a specially designed headset to expose the entire brain to low-intensity ultrasound waves for an hour-long treatment session.

The company is developing the treatment specifically for patients with brain tumors. A patient could receive the ultrasound during an outpatient session of intravenous chemotherapy, to open the blood-brain barrier and let the drugs into the brain. Kyle says it would be “a kinder and gentler way of delivering therapeutics to the brain” than current invasive methods, such as an infusion pump or a surgical implant. He also believes that his company’s approach would be better than focused methods when it comes to treating tumors that have spread to multiple parts of the brain, because it reaches the entire brain at once.  

Although Perfusion is initially developing the technique to treat primary brain tumors, the majority of brain cancers originate elsewhere and metastasize to the brain; in these cases, the technique might help deliver drugs designed for other kinds of cancer into the brain, Kyle says. He further believes the method could someday help treat other kinds of neurological disorders.

Nathan McDannold, a researcher at Harvard Medical School and Brigham and Women’s Hospital who has been developing focused ultrasound for drug delivery to the brain, agrees that if Perfusion Technology’s method is proved to work it will have advantages, because it doesn’t require microbubble agents and expensive equipment. But the company still needs to prove the safety and effectiveness of its approach. The biggest safety concern is bleeding: when a similar ultrasound method was tested on stroke patients several years ago as a way of dissolving clots, it led to excessive bleeding.

Kyle says his company has completed five animal studies over the past few years and has used its ultrasound technique to deliver several large molecules safely to the brain, including the cancer drug Avastin. The company hopes to complete preclinical animal studies in the next year and prepare for initial trials in humans.

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Credit: Courtesy of Al Kyle

Tagged: Biomedicine

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