Abstract
Alzheimer’s Disease (AD) embodies the complex coordination of neurodegeneration, neuroinflammation, and neurotoxic mediator responses of a multitude of neural cell types. Current animal models are limited in their representation of an in-vivo human response, cell numbers, and reproducibility. Thus, the use of AD patient-derived induced pluripotent stem cells (iPSCs) alongside reliable and reproducible differentiation methods allows for large-scale generation of more physiologically relevant in-vitro disease models to facilitate drug-discovery research progression.
At Axol Bioscience, we have access to an extensive library of fully consented AD patient donor samples with a variety of disease-causing mutations which enables us to capture the complexity of AD pathophysiology and facilitate mutation-specific AD research and drug-discovery development through a “Clinical Trial In A Dish”.
Neurodegenerative diseases (NDDs) such as Alzheimer’s Disease and Parkinson’s Disease are a leading cause of physical and cognitive disability, affecting around 15% of the global population [1]. With rising prevalence due to an aging population, there is a growing need for better, safer therapies and curative treatments. The cortex is a key area affected by NDD and is also a common site of drug-induced neurotoxicity (a leading cause of drug attrition), hence it is a major target for drug discovery [2]. However, the lack of physiologically relevant cortical models is a major challenge, with traditional animal models failing to translate from “bench to clinic” and low complexity afforded by simple cell culture and cell line models.
In partnership with Sumitomo Pharma America, Inc., Axol Bioscience performed a blinded study testing eight reference compounds on an isogenic cortical tri-culture axoModel, using an Axion multi-electrode array (MEA) system to measure electrophysiological response. Here we demonstrate robust identification of reference compound mode of actions, validating this axoModel for use in human-relevant drug discovery and neurotoxicity screening.
