Key Points
- A preclinical study at the University of Virginia found that focused ultrasound could stop cerebral cavernous malformations (CCMs) from growing.
- The results also suggest that the therapy helps prevent future CCMs from developing.
Researchers at the University of Virginia recently published results of a preclinical study testing the effects of focused ultrasound plus microbubble blood-brain barrier (BBB) opening on cerebral cavernous malformations (CCMs).
CCMs are abnormal clusters of dilated blood vessels in the brain, often resembling a raspberry. Though most CCMs are not symptomatic, they can leak and cause headaches, seizures, strokes, and can even be fatal. They can occur spontaneously, but they are also known to run in families. Current standard-of-care treatments include surgery to remove the lesion or stereotactic radiosurgery.
A research team led by Richard J. Price, PhD, co-director of UVA Health’s Focused Ultrasound Cancer Immunotherapy Center, used MR-guided low-intensity focused ultrasound combined with microbubbles to disrupt the BBB in a mouse model.
Once initial results proved that the focused ultrasound could safely disrupt the BBB in the subjects, the team proceeded with three different protocols in as many cohorts. They tested a single session of focused ultrasound, two or three sessions – depending on the ultrasound parameters – staged three days apart, and three sessions staged three days apart.
One month after treatment, 94% of the CCMs treated with focused ultrasound across all treatment cohorts had not grown. In comparison, CCMs that were left untreated had grown approximately seven times larger. Moreover, the mice treated with focused ultrasound were much less likely to develop new CCMs.
The team expounded upon these results, agreeing that current clinical focused ultrasound devices could theoretically treat CCMs in patients. However, further studies are required before this treatment could be applied to patients.
This study was developed based on results of a Foundation-funded study that tested an alternative mechanism of focused ultrasound for CCMs. Though that study proved unsuccessful, Dr. Price and his colleagues were able to use the preclinical model of CCMs that was developed as part of that initial study and alter the type of focused ultrasound used to achieve these positive results.
“This is a clear example of serendipity in science. We were looking for something else – performing long-term safety studies of focused ultrasound as a tool for drug and gene delivery to CCMs – when we noticed that CCMs exposed to focused ultrasound with microbubbles were being stabilized. After the initial observations, we spent years doing experiments to confirm the effect was real and reproducible,” said Dr. Price. “Because the focused ultrasound treatment is relatively simple and noninvasive – and the necessary clinical devices are becoming more common – if proven safe in clinical trials, I am hopeful it could eventually become a real treatment option.”
Read “Focused Ultrasound-Microbubble Treatment Arrests the Growth and Formation of Cerebral Cavernous Malformations” (Open Source) in Nature Biomedical Engineering