REBALANCE aims to discover the key cellular targets and molecular mechanisms underlying FUS-induced brain cleaning and therapeutic efficacy in AD. In addition, we further aim to combine FUS together with pharmacological activation of Piezo1. We will mechanistically link the cellular players and intracellular pathways responsible for the increase in BBB permeability, microglia-mediated Aß clearance and enhancement in glymphatic flow and evaluate the underlying molecular, cellular, and neuro-glia networks involved in the protection. The combination of human-based models and state-of-the-art animal models bridges the preclinical mechanistic findings to clinical data and provide biomarkers indicative of therapeutic benefit. Continuous analysis of ethical issues will allow us to identify ethical challenges in the R&D process from the point of view of different stakeholders, to minimize ethical risks and to involve patient organizations in the dialog.

2023

2027