Developing a neural spheroid model of amyotrophic lateral sclerosis for high-throughput drug screening

Authors

• M Carrasco
• J Zhang
• S Kundu
• E Lee
• M Ferrer

Abstract

Our group previously established a method for generating functional brain region-specific neural spheroids compatible with high-throughput screening (HTS). This platform can be manipulated to mimic different brain regions and model different diseased states, thereby serving as a robust tool for drug discovery. Building off this work, our goal herein is to develop a HTS-compatible neural spheroid model of amyotrophic lateral sclerosis (ALS) using iPSC-derived motor neurons and astrocytes to mimic the motor cortex of the brain. ALS is a fatal neurodegenerative disease with no cure and whose underlying mechanism is not fully understood. However, mutations in the transactivation response DNA-binding protein 43kDa (TDP-43) have been linked to ALS pathology. Therefore, we include genetically engineered motor neurons with TDP-43 mutations to model this diseased state. Using intracellular calcium activity as a functional readout, our first objective is to establish a baseline phenotype for wild type (WT) “healthy” motor neuron spheroids and validate using control compounds with known effects on different neuronal subtypes.

Scientific Focus Area: Neuroscience

This page was last updated on Monday, September 25, 2023