Key Points
- Repeated, extensive focused ultrasound–mediated blood-brain barrier opening (BBBO) on both frontal lobes is safe and potentially beneficial.
- The treatment decreased amyloid plaques in some patients and also showed improvement in one neuropsychiatric test.
- This study was led by Jin Woo Chang, MD, PhD, in Korea.
Results from a novel clinical trial (NCT06158789) using focused ultrasound to treat Alzheimer’s disease have now been published in the Journal of Neurosurgery. Jin Woo Chang, MD, PhD, a neurosurgeon at Korea University Anam Hospital in Seoul, Korea, conducted the Foundation-funded clinical trial from 2022 to 2023.
The study enrolled six participants, all women, aged 50 to 85 years. Dr. Chang designed the protocol to determine whether opening a larger volume of the blood-brain barrier (BBB) bilaterally and more frequently was as safe as opening smaller volumes in his previous studies. The BBB opening treatments were performed using intravenously injected DEFINITY® (perflutren lipid microsphere) microbubbles (Lantheus, N. Billerica, MA, USA) in combination with the Exablate Neuro 220 kHz low-intensity focused ultrasound system (Insightec, Inc., Haifa, Israel).
The focused ultrasound–mediated BBB opening volume in this study, as confirmed by contrast-enhanced MRI, averaged 43.1 cubic centimeters. This volume is twice as large as Dr. Chang’s first clinical trial and also larger than any clinical trials conducted by investigators from around the globe. The trial therefore exposed more of the amyloid in the brain to focused ultrasound than any previous study. This is an important milestone in the treatment of Alzheimer’s disease with focused ultrasound.
“We developed this protocol to provide optimal benefit and to test the technology in larger regions of the brain that are affected by Alzheimer’s disease,” said Dr. Chang. “This study begins to provide a more complete understanding of the effects of BBB opening alone. It will serve as the basis for future trials comparing any potential benefit of adding drug delivery the affected areas of the brain.”
Each of the six participants underwent BBB opening in both frontal lobes three times at 2-month intervals. The team used positron emission tomography (PET) to measure amyloid plaque levels and administered several cognitive tests before and after treatment. No medications were given as part of the treatment.
The focused ultrasound–mediated BBB opening was shown to decrease amyloid plaques in some participants. Compared with baseline, amyloid levels decreased in four patients (amyloid-decrease group) but increased in two (amyloid-increase group). Results demonstrated that not only did amyloid decrease in the areas treated with focused ultrasound but also showed a global longitudinal decrease in amyloid throughout the brain. Improvements were also observed in 5 of the 6 participants (83%), as measured by the Caregiver Administered–NeuroPsychiatric Inventory (CGA-NPI) score, a clinical measure of neuropsychiatric symptoms in patients with Alzheimer’s disease. All participants completed the study without any treatment-related adverse events.
“This study is critical to the field as a whole,” said Foundation Chairman Neal F. Kassell, MD. “Knowing what happens with blood-brain barrier opening in the absence of drugs in patients with Alzheimer’s disease adds a tremendous amount of knowledge to the field and lays the groundwork for further exploration with multiple focused ultrasound mechanisms of action. Focused ultrasound is a new technology that is now being explored in patients with Alzheimer’s disease, a field that has remained stagnant in terms of therapeutic options over the past several decades.”
In conclusion, repeated and more extensive (larger volume) focused ultrasound–mediated BBB opening on both sides of the frontal lobe was safe and potentially beneficial to patients with Alzheimer’s disease, even without the co-administration of any drugs.
Due to the findings reported in this article, a subsequent study is planned to investigate even larger volumes of focused ultrasound BBB opening and its effects. The Focused Ultrasound Foundation will also be funding the follow-up study.