Clinical trial of blood-brain barrier disruption by pulsed ultrasound
Sci Transl Med. 2016 Jun 15 ;8(343):343re2. PMID: 27306666
Alexandre Carpentier, Michael Canney, Alexandre Vignot, Vincent Reina, Kevin Beccaria, Catherine Horodyckid, Carine Karachi, Delphine Leclercq, Cyril Lafon, Jean-Yves Chapelon, Laurent Capelle, Philippe Cornu, Marc Sanson, Khê Hoang-Xuan, Jean-Yves Delattre, Ahmed Idbaih
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.
Article Published Date : Jun 14, 2016