Researchers at Northwestern University have trailed an implanted ultrasound device in patients, which is used in combination with microbubbles to transiently open pores in the blood brain barrier, allowing chemo drugs to enter. We have reported on this technique before as a lab-based concept (see flashbacks below), but this is the first time that it has actually been trialed in human patients, in this case patients with glioblastoma, a difficult to treat brain cancer. The approach successfully led to a four- to six-fold increase in chemo concentrations in the brain, using drugs that are not otherwise able to cross the blood-brain barrier, sparking hopes that the technique could pave the way for an effective treatment.
A microbubble/ultrasound combination has been proposed quite a while back as a way to open the blood brain barrier temporarily to allow certain drugs to enter the brain. While it has shown some promise in animal models, this is the first clinical trial that has shown that it may also work in humans. The stakes are high, as glioblastoma, the brain cancer which was the focus of the trial, currently has no effective treatments.
As a refresher, the concept involves administering a stream of microbubbles into the bloodstream, and then using ultrasound to make them vibrate as they pass through the blood vessels of the brain. This vibration causes transient pores to open in the specialized endothelium that lines these vessels, resulting in an exploitable weakness in the blood brain barrier. A chemotherapeutic administered into the bloodstream during this therapeutic window can then pass through these pores and access the brain.
This version of the technique actually involves implanting a grid of nine ultrasound emitters into the skull. The device was designed by designed by a French biotechnology company called Carthera. When activated, the emitters can bathe a significant portion of the brain in ultrasound. The trial involved glioblastoma patients who had had their tumor resected and the ultrasound device implanted during the same surgical procedure. Here’s an example video of the procedure:
Strikingly, the technique led to a marked increase in the amount of drug reaching the brain, with 4-6-fold increases observed for drugs such as paclitaxel, which is not usually administered for tumors that sit behind the blood brain barrier, as it cannot typically cross the barrier in significant quantities. “While we have focused on brain cancer (for which there are approximately 30,000 gliomas in the U.S.), this opens the door to investigate novel drug-based treatments for millions of patients who suffer from various brain diseases,” said Adam Sonabend, a researcher involved in the study.
See a video about the technology below:
Study in journal The Lancet Oncology: Repeated blood–brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial
Flashbacks: Ultrasound and Microbubbles Used to Penetrate the Blood-Brain Barrier; Short Wavelength Ultrasound Helps Drugs Get Inside Brain Safer; Focused Ultrasound and Microbubbles Push Drugs Across Blood-Brain Barrier; Temporarily Opening Up the Blood-Brain Barrier Using Ultrasound Waves