Imagine what modern medicine would be like without the ability to effectively and consistently administer drugs intravenously. That’s a good way to frame the huge delivery limitation that plagues neuroscience: Despite all the advances in drug discovery over the past decades, the biggest roadblock to treating brain cancers and other neurological diseases and disorders remains the brain’s own protective shield, the blood-brain barrier (BBB).
But what if the blood-brain barrier could be temporarily — and safely — overcome? A new approach, using ultrasound to open a “therapeutic window” in the BBB, is currently being tested in a pivotal trial for the aggressive brain cancer glioblastoma, putting us closer than ever to breaking through this roadblock.
This new strategy for drug delivery holds the potential not only to transform treatment outcomes for patients living with this deadly brain cancer, but also to fundamentally change what’s possible in brain medicine. By creating a universal platform for brain therapy delivery, this ultrasound-based approach could unlock new treatments across the entire spectrum of neurological disease.
Glioblastoma shows the frustrating limitations presented by the BBB
The brain’s natural shield, the BBB is remarkably effective in keeping toxins out. But in an ironic twist, that also means it prevents over 95% of small-molecule and 100% of large-molecule drugs from reaching their targets within the brain.
Glioblastoma (GBM) provides a stark example of the BBB challenge. It’s an aggressive, invasive brain cancer with historically poor outcomes. Even powerful chemotherapy drugs that show promise against GBM cells in the lab often fail in patients simply because these drugs cannot cross the BBB in sufficient concentrations to be effective. Patients and their families are left facing a harsh reality that’s hard to reconcile: We have the wonder drugs to save lives — we just can’t deliver them where they’re needed.
How ultrasound opens a “therapeutic window” in the BBB
The first-of-its-kind device at the heart of the pivotal phase 3 trial uses low-intensity pulsed ultrasound to safely overcome the BBB and temporarily create a crucial therapeutic window. The implant, which contains ultrasound transducers, is implanted beneath the scalp — typically during a tumor removal procedure.
When it’s time for treatment, microscopic bubbles are administered intravenously, and the device is activated for a few minutes. The gentle ultrasound waves cause the microbubbles circulating within the brain’s capillaries to vibrate. Because of their low intensity, these vibrating microbubbles are harmless to the brain — but they are enough to temporarily ‘loosen’ the tight connections of the BBB in the targeted area. This creates a therapeutic window that lasts several hours — allowing administered drugs to permeate brain tissue at a significantly and reliably higher concentration. The process is designed to be both safe and eminently repeatable to allow for multi-session therapy cycles.
Phase 3 trial uses glioblastoma as the proving ground for ultrasound-enhanced drug delivery
Recurrent glioblastoma — with its dire prognosis and treatments limited by the BBB — offers the ideal challenge for testing the clinical potential of this novel drug delivery method. Currently underway, the SONOBIRD trial follows promising results from earlier Phase 1 and 2 studies that established safety and feasibility and demonstrated enhanced drug delivery capabilities of the SonoCloud-9 device.
This large-scale, international Phase 3 pivotal trial has a simple objective with profound implications: Will using the SonoCloud-9 device to open the BBB immediately after administering the chemotherapy drug Carboplatin produce significantly better clinical outcomes for patients with recurrent GBM compared to standard chemotherapy alone? Success in the SONOBIRD trial would not only offer tremendous new hope for GBM patients and their loved ones but also provide broader clinical validation of the SonoCloud ultrasound platform as an effective way to safely overcome the BBB and enhance drug delivery to the brain.
A paradigm shift in brain medicine
Proving this technology in the face of deadly and difficult glioblastoma is the vital first step, but the clinical importance of reliably opening a therapeutic window in the BBB extends far beyond oncology.
This technology represents a potential “master key” that could unlock access to the brain for therapies previously stifled by the brain’s built-in protection. Promising drugs for neurological disorders like Alzheimer’s or Parkinson’s disease that failed only because they couldn’t cross the BBB could be revisited — and potentially brought rapidly into clinical practice. Researchers could finally examine the use of large-molecule biologics, antibodies or even gene therapies to effectively target neurological diseases. This treatment delivery platform could transform therapies for everything from multiple sclerosis and Huntington’s disease to brain metastases and genetic disorders.
The commencement of this pivotal Phase 3 trial puts us remarkably close to realizing these transformational outcomes. By finally solving one of the most fundamental and frustrating problems in modern drug delivery, this pioneering technology is poised to usher in a new era where we can double down on developing and advancing powerful drug therapies to move brain medicine forward.
About the Author
Michael Canney, Ph.D., is Chief Scientific Officer at Carthera, a clinical-stage medtech company advancing brain therapy through innovative ultrasound-based devices. A co-author of more than 50 peer-reviewed articles, he specializes in neuro-oncology, glioblastoma and neurodegenerative diseases. At Carthera, he is responsible for leading scientific collaborations with academic institutions, organizing U.S. clinical trials and more.
