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Implanted Ultrasound Lets Chemo Access Brain |Published May 12, 2023

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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

Via: Northwestern

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Implanted Ultrasound Lets Chemo Access Brain |

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Researchers at Northwestern University have trailed an implanted ultrasound device in patients, which is used in combination with microbubbles to

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Utilization of implantable ultrasound devices, in conjunction with microbubbles, allows chemo to cross the blood brain barrier, targeting previously poorly treated brain cancers. The vibration of the microbubbles creates small openings in the vascular structures, allowing the brain to be coated in ultrasound waves. Through these tiny openings chemotherapeutic agents are able to cross the blood brain barrier and target previously unreachable cancerous cells. A four to six fold increase of chemotherapy concentrations in the brain were observed in animal trials performed (Hastings, 2023).

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Ultrasound Opens Blood Brain Barrier to Let In Cancer Drugs

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Pros:

Improvement in ability to deliver chemotherapy to previously unreachable brain tumors.

Multiple doses can be administered over several weeks

The device is biodegradable over 6 weeks, preventing need for further risky surgeries to remove (Prillaman, 2023).

Cons:

Device coating is made of glycine, which dissolves quickly in water creating extra production steps to ensure stability of the product (Prillaman, 2023).

Device degrades over 6 weeks, leaving a short time period for adequate therapy (Prillaman, 2023).

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The ability to deliver targeted chemotherapy to difficult to treat brain tumors opens the door for development of new treatment pathways for various brain cancers. With greater than 30,000 glioma cases in the United States, this pathway for treatment creates hope for advancement of treatment in other brain disorders and cancers.

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Communication: Presents information and ideas easily and clearly

Responsibility: Stability, will follow through and take ownership of commitments

Activator: take ideas and turn them into reality

Consistency: Fair with all team members and participants

Command: Ability to make decisions

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Andrew: Activator – Self-starter, will turn ideas in to reality, will help guide decision-making process

Alice: Achiever – Strong work ethic and will help keep forward momentum in project development

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Gallup. (2023, August 8). What are the 34 CliftonStrengths themes?. Gallup.com. https://www.gallup.com/cliftonstrengths/en/253715/34-cliftonstrengths-themes.aspx

Hastings, C. (2023, May 12). Implanted ultrasound lets chemo access brain |. Medgadget. https://www.medgadget.com/2023/05/implanted-ultrasound-lets-chemo-access-brain.html

Prillaman, M. (2023, May 4). Ultrasound allows a chemotherapy drug to enter the human brain. Science News. https://www.sciencenews.org/article/ultrasound-chemotherapy-drug-human-brain#:~:text=A%20study%20shows%20how%20pairing,drug%20to%20enter%20 the %20organ.

YouTube. (2023). YouTube. Retrieved September 20, 2023, from https://www.youtube.com/watch?v=swYviF0ucK0.