Dr Rinie Bajracharya, UQ : "Tau immunotherapy: mechanistic studies into a novel anti-tau antibody and its therapeutic potential in combination with ultrasound"
Speaker:
Dr Rinie Bajracharya
Queensland Brain Institute
University of Queensland
Title: "Tau immunotherapy: mechanistic studies into a novel anti-tau antibody and its therapeutic potential in combination with ultrasound"
Abstract:
After almost 20 years with no drug approvals for Alzheimer’s disease, a monoclonal antibody against amyloid-beta (Aβ), Aducanumab, was approved by the FDA, despite uncertainties about its effectiveness. In fact, several members of the prestigious FDA panel resigned over the approval this June. Over recent years, tau, the second histopathological hallmark of Alzheimer’s disease, has entered the limelight as an alternative therapeutic target for immunotherapy. Currently, several tau immunotherapies are undergoing human clinical trials. However, targeting tau effectively remains a considerable challenge due to 1) the intraneuronal localisation of tau and 2) the restrictive nature of the blood-brain barrier (BBB), which excludes 99.8% of peripherally administered antibodies. Thus, efforts to ensure that tau immunotherapies do not follow the same fate as Aβ immunotherapies is paramount. We have previously shown that intravenous injections of microbubbles followed by the application of scanning ultrasound (SUS+MB) can transiently open the BBB, allowing an up to 19-fold increase in IgG antibody uptake into the brain. However, a microscopic analysis of the therapeutic efficacy and brain localisation of tau-specific IgG antibodies has not yet been explored following enhanced brain delivery. To investigate this, tau transgenic K3 mice were passively immunised with our novel in-house pan-tau antibody, RNF5, in combination with or without SUS+MB. Our new findings reveal the complexities of combining tau immunotherapy with ultrasound and challenge the view that this is a straight-forward approach.
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Neuroscience seminars at the QBI play a major role in the advancement of neuroscience in the Asia-Pacific region. The primary goal of these seminars is to promote excellence in neuroscience through the exchange of ideas, establishing new collaborations and augmenting partnerships already in place.
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