The Babraham Distinguished Seminar Series is sponsored by the Babraham Institute and the Babraham Research Campus which is home to more than 50 biotech companies. The seminars are also advertised to the wider Cambridge community. The series will provide exciting science talks by distinguished scientists from across the world in many areas of biomedical interest. Followed by the talk will be tea, coffee, cake and networking.
Prof Jürgen Götz; The University of Queensland, Australia
Professor Jürgen Götz is the Lesleigh Green - Bill and Nancy Green Endowed Chair in Dementia Research and inaugural Director of the Clem Jones Centre for Ageing Dementia Research (University of Queensland). Professor Götz studied biochemistry in Switzerland and earned his PhD in immunology with Nobel Laureate Köhler in Germany. After postdoctoral work at UCSF and at Novartis, he became a group leader in Zürich, before moving to the University of Sydney in 2005, and then to the University of Queensland (Queensland Brain Institute) in 2012. A major focus of his laboratory is to gain insight into how tau and amyloid both separately and synergistically contribute to Alzheimer’s disease. In recent years, the laboratory has started to develop therapeutic ultrasound into a treatment modality for Alzheimer’s disease and other brain diseases, both by transiently opening the blood-brain barrier and as a neuromodulatory tool. The team has built an investigational device under ISO13485 guidelines and already completed a safety trial. Professor Götz has published more than 230 papers in leading journals including Cell, Science and Neuron, and has authored many authoritative reviews in the Nature Reviews journal family.
Ultrasound is a therapeutic modality that is increasingly being explored both as a neuromodulatory and blood-brain barrier (BBB)opening tool, the latter to facilitate targeted and effective drug delivery to the brain. A decade ago, we initiated a program of applying this technology to Alzheimer’s disease, performing studies in mice and sheep, building a clinical trial ready device, and initiating a safety study in Alzheimer’s disease (AD) patients. We use two types of low-intensity ultrasound modalities, scanning ultrasound (SUS)delivered together with microbubbles to achieve BBB opening (SUS+MB), and SUS delivered without microbubbles to achieve neuromodulation (SUS only). These modalities were applied to mouse models of senescence and Alzheimer’s disease, and this preclinical work informed our clinical trial design. More specifically, we explored SUS+MB and SUS only over a range of ultrasound parameters in amyloid-depositing APP23 mice and senescent wild-type mice, with several weekly treatment sessions. Analysis tools included an extensive behavioural, electrophysiological, biochemical, histological, proteomics and imaging (MRI) analysis. We found that SUS+MB reduces amyloid pathology and restores cognition, that BBB opening is required for amyloid clearance and that, interestingly, SUS only is sufficient to restore cognition even in the absence of amyloid reduction. We further found that both SUS+MB and SUS only restore deficits in long-term potentiation (LTP) and improve cognition in senescent mice via pleiotropic mechanisms potentially converging on NMDAR-dependent signalling. With this insight, we have built a clinical-trial ready ultrasound device and completed a clinical trial in 12 AD patients using SUS only, demonstrating safety and tolerability. We are currently getting ready for a follow-up trial in AD, addressing the behavioural and psychological symptoms of dementia (BPSD). These activities are complemented by us developing anti-tau antibodies to restore Proteostasis. We further deliver these antibodies using SUS+MB and are currently optimising the antibodies to improve neuronal uptake. We conclude that therapeutic ultrasound is a non-invasive modality for the treatment for AD and other brain diseases. We also conclude that this modality has the potential of cognition enhancement in physiological ageing.
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