A novel protein-protein interaction inhibitor to treat Alzheimer’s disease

Alzheimer’s disease (AD) is the emerging health crisis of an aging population. Unfortunately, effective treatments for AD are lacking. Removing pathogenic protein deposits from the brain has failed to deliver a disruptive therapy. Hence, alternative therapeutic targets urgently need to enter clinical translation. Over the past decade, we have discovered a specific synaptic protein complex that governs neurotoxicity in AD and established strong proof-of-concept for inhibiting this complex therapeutically. Accordingly, our genetic therapy approach modulating this neurotoxic signalling pathway has been licensed to a biotech spin-off for commercialization.

Aiming at transforming this approach into an orally available CNS-active candidate drug lead for AD, we have resolved the detailed protein-protein interactions (PPIs) involved in the neurotoxic signalling pathway and used this insight to develop an artificial intelligence-assisted platform to screen large numbers of potential specific PPI inhibitors. This Development Grant proposes taking the lead compound from this platform that was validated as most efficiently mitigating neurotoxicity in AD models and establish critical data required for translation. This will involve demonstrating target engagement, tolerability and dose-effect relationship in established AD mouse models.

We will prepare documentation to engage with regulatory authorities to ensure alignment with requirements for a future Investigational New Drug (IND) application. In summery, this Development Grant will accelerate the translation of a novel PPI inhibitor towards commercial and clinical translation to eventually benefit those living with dementia.