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Sci Transl Med. 2016 Jun 15;8(343):343re2. doi: 10.1126/scitranslmed.aaf6086.

Clinical trial of blood-brain barrier disruption by pulsed ultrasound.

Author information

1
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires La Pitié-Salpêtrière, Service de Neurochirurgie, F-75013 Paris, France. Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013 Paris, France. alexandre.carpentier@aphp.fr.
2
CarThera, Institut du Cerveau et de la Moelle épinière (ICM), Paris F-75013, France.
3
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires La Pitié-Salpêtrière, Service de Neurochirurgie, F-75013 Paris, France. Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013 Paris, France.
4
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires La Pitié-Salpêtrière, Service de Neurochirurgie, F-75013 Paris, France.
5
AP-HP, Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, Service de Neuroradiologie, F-75013 Paris, France.
6
INSERM, U1032, LabTau, Lyon F-69003, France.
7
Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013 Paris, France. INSERM, U 1127, F-75013 Paris, France. CNRS, UMR 7225, F-75013, Paris, France. ICM, F-75013 Paris, France. AP-HP, Hôpitaux Universitaires La Pitié-Salpêtrière-Charles Foix, Service de Neurologie 2-Mazarin, F-75013 Paris, France.

Abstract

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.

PMID:
27306666
DOI:
10.1126/scitranslmed.aaf6086
[Indexed for MEDLINE]

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