Blood-Brain-Barrier Opening Device Enhances Chemotherapy Drug Delivery to Brain Tissue

The blood-brain barrier (BBB) presents a significant challenge in treating gliomas, a type of diffuse tumor that infiltrates the peri-tumoral normal brain. This barrier prevents over 95% of small-molecule drugs and all large-molecule drugs from entering the brain, thus reducing their therapeutic impact. Now, an implantable device utilizes the power of pulsed ultrasound to temporarily open the BBB. This provides a window period during which drug therapies can be administered and can reach the brain in higher and more effective concentrations when the BBB is disrupted.

Carthera’s (Lyon, France) SonoCloud device is designed to be implanted in a skull window beneath the skin, remaining invisible from the outside. When activated for a few minutes via a transdermal needle connected to an external control unit, the device employs low intensity pulsed ultrasound (LIPU) to breach the BBB for several hours. This window of opportunity allows for the administration of drug therapies. The concept of using LIPU to disrupt the BBB has been under pre-clinical development for over two decades. The technology leverages low-intensity ultrasound, akin to levels used in diagnostic imaging, in conjunction with an intravenous microbubble agent to stimulate a therapeutic effect. The LIPU causes the injected microbubbles in brain microvessels to vibrate, mechanically disrupting the BBB’s tight junctions, enhancing active transport across the BBB, and reducing active drug efflux transporters.

Carthera has developed multiple versions of the SonoCloud device, including SonoCloud-1 and SonoCloud-9. These MRI-compatible devices are engineered to disrupt large regions of the BBB, aiming to improve the therapeutic efficacy of drugs in specific brain areas. Currently, these devices are undergoing clinical trials for glioblastoma, brain metastases, and Alzheimer’s Disease. Carthera has initiated the SONOBIRD clinical trial, an open-label, comparative, randomized, multicenter study with a two-arm design and a 1:1 ratio. This trial will assess the overall survival of glioblastoma patients treated with carboplatin chemotherapy in conjunction with the SonoCloud-9 system to breach the BBB. Outcomes will be compared against standard regimens recommended by medical consensus, such as lomustine or temozolomide. Additionally, the trial aims to evaluate the effectiveness of the SonoCloud-9 and carboplatin treatment in delaying or reducing tumor growth.

“The launch of the SONOBIRD trial is a significant achievement in the clinical development of the SonoCloud-9 system. If the efficacy of carboplatin in combination with our device is proven, it will change the paradigm of how we treat glioblastoma,” said Carole Desseaux, chief clinical officer at Carthera