Poster #073
Modeling Riluzole Response in C9orf72-ALS Spinal Cord Organoids
Mentors: Alba Sansa Zaragoza, PhD and Clive Svendsen, PhD
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease marked by glutamate-mediated excitotoxicity and motor neuron loss. We generated spinal cord organoids (ScOs) from human induced pluripotent stem cells (hiPSCs) derived from a healthy control and a C9orf72 ALS patient (C9ALS), using a protocol adapted from Sansa et al. (2023). Over 60 days in vitro, ALS-derived ScOs remained smaller than controls, indicating impaired growth or organization. To test whether Riluzole, which reduces excitotoxicity by modulating glutamate signaling, could rescue this phenotype, we treated both groups with varying doses over time. In both control and ALS-derived ScOs, 1 µM Riluzole supported steady growth comparable to untreated ScOs, while higher concentrations (5 and 10 µM) resulted in slower growth rates. These findings highlight the utility of ScOs for modeling ALS, although further investigation of Riluzole as a therapeutic for C9ALS-associated ALS would be needed.