Researchers at UVA Health have developed a promising non-invasive treatment for cerebral cavernous malformations (CCMs) that uses focused ultrasound technology to halt the growth of these potentially dangerous brain lesions. The technique, which requires no drugs or surgical intervention, showed remarkable efficacy in laboratory testing, arresting growth in 94% of lesions after just one month of treatment.
CCMs are clusters of abnormal blood vessels that can develop in the brain, spinal cord, or other parts of the body. While often asymptomatic, these lesions can cause severe neurological problems including headaches, seizures, muscle weakness, and in some cases, fatal brain hemorrhages.
Serendipitous Discovery Leads to Treatment Breakthrough
The treatment approach was discovered unexpectedly during safety studies of focused ultrasound for drug and gene delivery. Richard J. Price, PhD, co-director of UVA Health's Focused Ultrasound Cancer Immunotherapy Center, explained the fortuitous finding.
"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 just focused ultrasound with microbubbles were being stabilized," said Price.
The technique employs tiny gas-filled microbubbles propelled by focused ultrasound waves to temporarily open the blood-brain barrier, the protective layer surrounding the brain. This process appears to inhibit the progression of CCMs through mechanisms that researchers are still working to fully understand.
Impressive Preclinical Results
In mouse models, the results were striking. While untreated lesions increased in size seven-fold over one month, 94% of lesions treated with the ultrasound-microbubble approach showed no growth during the same period. Notably, the mouse models used in the study present a more aggressive form of CCM than typically seen in humans, suggesting the treatment might be even more effective in clinical applications.
The research team also observed that treated brain tissue appeared less likely to develop new CCMs, indicating a potential preventive effect. This could be particularly beneficial for patients with familial CCM, who are genetically predisposed to developing multiple lesions over time.
Advantages Over Current Treatment Options
Current CCM treatments include brain surgery, typically reserved for lesions at high risk of bleeding, and stereotactic radiosurgery, which targets hard-to-reach lesions with radiation. Both approaches carry significant risks.
"Surgical interventions can lead to complications, and there's always the possibility that removed CCMs may regrow," explained Price. "Radiation therapy has its own set of potential side effects. Our approach offers a completely non-invasive alternative that could avoid these complications."
The new ultrasound technique is particularly promising because the necessary devices are increasingly available in clinical settings, potentially making the treatment accessible to more patients once approved.
Path to Clinical Implementation
Simulated treatment plans using existing stereotactic radiosurgery patient data suggest that this method is feasible with current technology. However, clinical trials will be necessary before regulatory approval can be sought.
"We're optimistic about translating these findings to human patients," said Price. "The technology exists, and our preclinical results are compelling. The next step is designing appropriate clinical trials to demonstrate safety and efficacy in patients."
Mechanism and Future Research Directions
Unlike many therapeutic approaches, this technique does not rely on pharmaceutical interventions. Focused ultrasound with microbubbles has previously been investigated to transiently open the blood-brain barrier for improved drug delivery in diseases such as Alzheimer's. Interestingly, in both Alzheimer's and CCM research, the ultrasound-microbubble interaction alone appears to produce therapeutic effects.
Ongoing research at UVA Health aims to clarify precisely how focused ultrasound inhibits CCM growth and to explore combining this baseline effect with drug or gene therapies to potentially eliminate lesions completely rather than just halting their growth.
The development builds on UVA's substantial investment in focused ultrasound technology and its extensive expertise in this field. The research was recently published in Nature Biomedical Engineering, highlighting its significance in the medical community.
For patients with CCMs, particularly those with the familial form who may develop multiple lesions throughout their lifetime, this non-invasive approach could represent a significant advance in treatment options, potentially reducing the need for repeated surgeries or radiation exposure.
