Clinical trial of blood-brain barrier disruption by pulsed ultrasound

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Science Translational Medicine  15 Jun 2016:
Vol. 8, Issue 343, pp. 343re2
DOI: 10.1126/scitranslmed.aaf6086

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A sound attack on brain tumors

Brain tumors are difficult to treat with chemotherapy because the blood-brain barrier greatly limits the delivery of drugs into the brain. Carpentier et al. have developed a pulsed ultrasound device, which they implanted into the skull of patients with glioblastoma, an aggressive and difficult to treat brain tumor, in a first-in-human trial. At regularly scheduled treatment sessions, the researchers activated the ultrasound device by connecting it to a power source, disrupting the blood-brain barrier long enough for subsequent chemotherapy to reach the brain. The authors confirmed that this approach was well tolerated and showed evidence of effectiveness to disrupt the blood-brain barrier, paving the way for further development of this therapeutic approach.


The blood-brain barrier (BBB) limits the delivery of systemically administered drugs to the brain. Methods to circumvent the BBB have been developed, but none are used in standard clinical practice. The lack of adoption of existing methods is due to procedural invasiveness, serious adverse effects, and the complications associated with performing such techniques coincident with repeated drug administration, which is customary in chemotherapeutic protocols. Pulsed ultrasound, a method for disrupting the BBB, was shown to effectively increase drug concentrations and to slow tumor growth in preclinical studies. We now report the interim results of an ultrasound dose-escalating phase 1/2a clinical trial using an implantable ultrasound device system, SonoCloud, before treatment with carboplatin in patients with recurrent glioblastoma (GBM). The BBB of each patient was disrupted monthly using pulsed ultrasound in combination with systemically injected microbubbles. Contrast-enhanced magnetic resonance imaging (MRI) indicated that the BBB was disrupted at acoustic pressure levels up to 1.1 megapascals without detectable adverse effects on radiologic (MRI) or clinical examination. Our preliminary findings indicate that repeated opening of the BBB using our pulsed ultrasound system, in combination with systemic microbubble injection, is safe and well tolerated in patients with recurrent GBM and has the potential to optimize chemotherapy delivery in the brain.

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