From the April 2019 issue of HealthCare Business News magazine

Over the last decade several pivotal preclinical studies have demonstrated that FUS can be used as a potential therapeutic delivery strategy, and even, perhaps, as a stand-alone therapy itself. The teams of Dr. Hynynen and Dr. Isabelle Aubert, also a scientist at Sunnybrook, have shown that FUS-mediated BBB opening dramatically enhances brain concentration of anti-amyloid antibodies in preclinical models, leading to increased clearance of amyloid pathology in affected regions. Surprisingly, these preclinical studies showed that temporarily opening the BBB, even without the co-delivery of a therapeutic, led to increased amyloid clearance, the generation of new neurons in the hippocampus (neurogenesis) and behavioural improvements on a memory task. This preclinical research demonstrated that opening the BBB generates a localized immune response that may permit the body’s own immune system to target and clear amyloid plaques. These exciting findings were further corroborated by work done by the group of Dr. Jurgen Gotz at the Queensland Brain Institute in Australia, showing ultrasound in transgenic AD models can be used to safely open the BBB, and clear amyloid, and potentially tau as well, either with ultrasound alone, or with the delivery of a therapeutic.

Continued research and beyond
Our group at Sunnybrook developed the first-ever clinical trial to investigate the safety of opening the BBB with FUS in patients with mild-to-moderate AD and involved targeting a small region in the frontal lobe. In this phase I trial, six patients were each treated twice, one month apart, in progressively larger volumes. We showed that temporarily opening the BBB in this region was well-tolerated by patients, safe, and not associated with bleeding, swelling or any untoward effects on memory, cognition or amyloid load in the brain. We further demonstrated that closure of the BBB happened in all cases, within 24 hours. For the first time in AD, the BBB could be breached noninvasively, in a highly controlled and precise fashion.

In AD, there is an ongoing phase II trial at Sunnybrook supported by the Weston Brain Institute and the Focused Ultrasound Foundation, where the goal is to open the BBB in multiple brain regions known to be involved in memory and cognition, and which are affected by amyloid pathology. These regions will be selected through 18F florbetaben PET scans allowing us to adopt a more personalized approach to both study design and eventually, treatment itself, permitting drug delivery in subsequent trials directly to where the pathology is located.

April 2019 Magazine

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