Patient-derived induced pluripotent stem cell organoids for amyotrophic lateral sclerosis drug discovery

Abstract

Complex biological mechanisms and unidentified therapeutic targets for amyotrophic lateral sclerosis (ALS) significantly hinder the development of effective treatments. Given these challenges, reliable disease models that accurately replicate ALS phenotypes with relevant biological underpinnings are essential for advancing precision medicine in ALS. Patient-derived induced pluripotent stem cell (iPSC) organoids have emerged as an innovative tool for disease modeling and drug evaluation. Growing evidence highlights the advantages of organoids in replicating ALS phenotypes and supporting drug development. However, challenges remain in utilizing organoids for ALS drug testing and other neurodegenerative diseases. In this review we summarize the current progress in ALS model development, encompassing both in vitro and in vivo non-human models, as well as iPSC-derived human models. Furthermore, within the context of ALS drug screening, we discuss critical considerations for applying organoids to evaluate disease-associated phenotypes and to accurately reflect disease-related symptoms.

Keywords

Amyotrophic lateral sclerosis / Disease models / Organoids / High-throughput screening

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