Neurology Daily Report: 01/182024

A Phase 1 clinical study investigated the effect of a portable focused ultrasound (FUS) system with real-time 2D microbubble cavitation mapping in 6 patients with mild to moderate Alzheimer's disease (AD) (1). The study found that blood-brain barrier opening (BBBO) was achieved in 5 out of 6 subjects, with an average volume of 983±626 mm3 following FUS at the right frontal lobe. The outpatient treatment was completed within 34.8±10.7 minutes. Cavitation dose correlated significantly with BBBO volume (R2>0.9, N=4), demonstrating the system's capability of predicting opening volumes. Larger opening volumes were associated with increased levels of AD biomarkers, including Aβ42/Aβ40 (R2=0.74), Tau (R2=0.95), and P-Tau181 (R2=0.86), assessed in serum-derived extracellular vesicles (EVs) sampled 3 days after FUS (N=5). From PET scans, subjects showed a lower Aβ load increase in the treated frontal lobe region compared to the contralateral region. Reduction in asymmetry standardized uptake value ratios (SUVR) correlated with the harmonic cavitation dose (R2>0.9, N=3). No additional changes were observed in the mini-mental state examination over 6 months as a result of FUS.

Reference

Bae S, Liu K, Pouliopoulos AN, Ji R, Jimenez-Gambin S, Yousefian O, Kline-Schoder AR, Batts A, Kokossis D, Mintz A, Honig LS, Konofagou EE. Transcranial Blood-Brain Barrier Opening in Alzheimer's Disease Patients Using A Portable Focused Ultrasound System with Real-Time 2-D Cavitation Mapping. medRxiv [Preprint]. 2024 Jan 18:2023.12.21.23300222. doi: 10.1101/2023.12.21.23300222. PMID: 38196636; PMCID: PMC10775403.