Leader:

The blood-brain barrier (BBB) remains the bottleneck for pharmacological therapy of neurological diseases, costing billionsto our societies.The goal of our team isto provide new solutionsto deliver drugsto the brain in a safe way in order to increase their efficacy on the target.Transcranial focused ultrasound isa particularly promising technique to transiently and locally disrupt thisvascular barrier. Since 2010,we use neuroimaging to characterize the technology and to develop translational strategies. We now aim at making it a reality for the highest possible number of patients in the future years.

In the last years, our team has pursued technological developments as well as preclinical proof of concept studies in collaboration with several other academic labs. Our work has led to >21peer reviewed publications related to ultrasound-aided drug delivery in international journals since 2018. We have worked on the impact of the transient BBB disruption on efflux transporters, and on neuro-inflammation. To be able to better model drug delivery, we have measured the diffusion properties of nanoparticles after their crossing of the BBB. On the technological side, we have implemented passive cavitation detection and feedback loop monitoring at high frame rate to ensure safety of the ultrasound procedure with a patented approach. We also introduced safe large volume BBB opening sequences for applications such as whole brain or hemispherical drug delivery.

Regarding applications, we have demonstrated the interest of the technique in small animal models, mainly in neuro-oncology, Alzheimer’s disease and gene delivery fields. We showed the capabilities to increase significantly the local concentration of MRI contrast agents and PET tracers, of drug-loaded nanoparticles, of therapeutic antibodies and of adeno- associated viruses. To translate this to patients, we have built a public-private French consortium to design, assemble, and test a new prototype of clinical device. This system is robotized and neuro-navigated to make it widely spreadable in hospitals. It is cost-effective and compatible with short ambulatory procedures in order to perform chronic sessions over months or years. During the course of this project, every technological feature has been validated in non-human primates. We now want to pursue its clinical development through a spin-off company.