Ultrasound implant safely opens blood-brain barrier in patients | June 20, 2016 Issue - Vol. 94 Issue 25 | Chemical & Engineering News
Volume 94 Issue 25 | p. 6 | News of The Week
Issue Date: June 20, 2016 | Web Date: June 17, 2016

Ultrasound implant safely opens blood-brain barrier in patients

New method could help anticancer drugs reach brain tumors
Department: Science & Technology
News Channels: Biological SCENE
Keywords: drug delivery, cancer, blood-brain barrier, ultrasound
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The SonoCloud implant sits fixed in a patient’s skull, under the skin. During an ultrasound treatment, a needle inserted through the skin transmits power to the device, allowing it to generate ultrasound waves into brain tissue.
Credit: Sci. Transl. Med.
An illustration of an implant that transmits ultrasound into a patient’s brain.
 
The SonoCloud implant sits fixed in a patient’s skull, under the skin. During an ultrasound treatment, a needle inserted through the skin transmits power to the device, allowing it to generate ultrasound waves into brain tissue.
Credit: Sci. Transl. Med.

The cells lining blood vessels in the brain form tight, tough-to-penetrate junctions that prevent toxic molecules from slipping into the brain.

Unfortunately, this blood-brain barrier also blocks cancer drugs from reaching tumor cells in the brain, creating a significant drug-delivery problem.

Now, preliminary results from a Phase I/II clinical trial suggest that a small implant that emits ultrasound waves can safely open the blood-brain barrier in people, potentially allowing drugs in (Sci. Transl. Med. 2016, DOI: 10.1126/scitranslmed.aaf6086).

Scientists have previously tested ultrasound methods in animals and found that the techniques can aid drug delivery to the brain. These methods often rely on injecting microbubbles—typically fluorinated gases encapsulated in lipid spheres. The sound waves cause these bubbles to expand and compress. That mechanical energy helps loosen the junctions between endothelial cells lining blood vessels.

To translate such a treatment into people, the company CarThera, founded by Alexandre Carpentier, a neurosurgeon at Pitié-Salpêtrière Hospital, in Paris, developed SonoCloud, an 11.5-mm-diameter ultrasound transducer that surgeons can implant in a hole in patients’ skulls. Carpentier envisions a brain-cancer patient receiving such an implant after a tumor biopsy or a surgery to remove parts of a tumor.

In the new study, the team reported data from 15 glioblastoma patients who had received the implant. Before these patients were treated with the cancer drug carboplatin, they received a 2.5-minute ultrasound session.

By using magnetic resonance imaging to watch a gadolinium contrast agent enter the brain, the researchers found that these sessions opened the blood-brain barrier. And the patients didn’t experience adverse effects from the ultrasound—no signs of hemorrhaging, no complaints of pain, and no indications that speech or motor control was disrupted.

CarThera will start a Phase III trial in 2017 to assess how ultrasound treatments can improve chemotherapy for brain cancer patients. Also, Carpentier is interested in determining if the device can help treat Alzheimer’s disease. Some studies in animals suggest that ultrasound can clear out toxic protein plaques from the brain, in part, by temporarily opening the blood-brain barrier.

Nathan McDannold of Harvard Medical School says the clinical trial data are an impressive milestone for the ultrasound therapy field. He is working on similar methods that don’t rely on an implant and instead use an external array of 1,000 ultrasound transducers to focus on a target in the brain. So, he says, although the SonoCloud is more invasive, it is a simpler system.

 
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Comments
Richard (June 17, 2016 11:36 PM)
I guess the remaining question is how many other substances, toxic or not, make it into the brain during the ultrasound treatment. I don't believe the brain has a working metabolism for these compounds, which might also work as neurotransmitters on a prolonged treatment with accumulation. After all, the barrier is there for a reason.

When I was a grad student, we had lectures about such brain implants, which could be filled from the outside and distribute drugs when needed. This was a precise treatment. Now we have new techniques which open all doors to get in one drug among hundreds of other compounds. I can't see progress, really.
Eric Faust (October 28, 2016 10:43 AM)
The issues of metabolic breakdown of pharmaceuticals or possible intrusion by other substances, even disease vectors during treatment is far less relevant than the fact that these patients are dying! Survival is short for the most part in gliomas, particularly intrinsic diffuse pontine glioma, for which there are now no effective treatment options. Without a method such as this of opening the blood brain barrier, chemotherapies don't work well. The sooner this is used with chemotherapeutic treatment of DIPG, especially in dying children for whom there is presently little hope, the better.

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