Alzheimer’s disease (AD) is expected to reach a global prevalence of 65.7 million by 2030, underscoring the urgent need for novel, safe and effective therapies. MR-guided Focused Ultrasound (MRgFUS) is a non-invasive neurosurgical modality, that when coupled with intravenously injected microbubbles (MB), has been found to effectively and temporarily open the blood-brain barrier (BBB). Our group has shown in animal AD models, that MRgFUS-mediated BBB opening at the hippocampus: i) is safe and reversible, ii) can be used to enhance delivery of anti-amyloid antibodies, and iii) can lead to focal reduction of amyloid with BBB opening alone, with concomitant improvement on memory tasks. Leveraging this pre-clinical data, we have now successfully completed the world’s first phase I feasibility trial of MRgFUS BBB opening in human patients with amyloid-positive AD.
The objective of this project is to extend our pilot work to a phase II trial with the goals of continued safety assessment at a novel target specific to memory function, as well as identifying and measuring clinical, radiographic and other biomarkers of response. This work has two central hypotheses: i) MRgFUS-MB can safely, transiently, and repeatedly open the BBB in bilateral hippocampi of patients with mild to moderate AD; and, ii) BBB opening will lead to detectable alterations in AD-specific clinical and imaging biomarkers.
This study aims to enroll 30 participants, who undergo repeated bilateral hippocampii BBB disruption using low frequency MRIgFUS. Baseline PET and CSF markers for amyloid and tau will be obtained. Participants will be followed for 6 months following the third and final procedure. This study is currently undergoing research ethics review and is targeted to begin in May 2018, pending regulatory approvals. Funding is pending and will be sought from Weston Brain Institute and Focused Ultrasound Foundation.