Abstract

Developing Preclinical and Clinical Biomarkers to Aid in Translation of Drug Therapies for Alzheimer’s Disease

Michael J. O'Neill, Senior Research Advisor, Head of Neurodegeneration Group, Eli Lilly & Co

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterised by extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs), with the latter being composed of microtubule-associated protein tau. In recent year various disease modifying approaches that target amyloid (including small molecule BACE and gamma secretase inhibitors and various biomolecule immunotherapy approaches) and interventions to block pathological tau accumulation (kinase inhibitors, tau aggregation inhibitors or immunotherapy approaches) have been developed and advanced as potential disease modifying agents. Clinical trials to show these disease modifying actions are long and expensive and often the clinical evidence is not gained until large (3-4yr) Phase III trials are completed.  It is therefore critical to have some translational biomarkers in early clinical development for these programs to ensure that there is target engagement, a clear pharmacodynamic and/or pharmacological effects of the molecule and ensure that the doses taken forward to Phase III will test adequately test the hypothesis