Human stem cell models of neurodegeneration: From basic science of amyotrophic lateral sclerosis to clinical translation

Abstract

Neurodegenerative diseases are characterized by progressive cell loss leading to disruption of the structure and function of the central nervous system. Amyotrophic lateral sclerosis (ALS) was among the first of these disorders modeled in patient-specific iPSCs, and recent findings have translated into some of the earliest iPSC-inspired clinical trials. Focusing on ALS as an example, we evaluate the status of modeling neurodegenerative diseases using iPSCs, including methods for deriving and using disease-relevant neuronal and glial lineages. We further highlight the remaining challenges in exploiting the full potential of iPSC technology for understanding and potentially treating neurodegenerative diseases such as ALS.

Keywords: ALS; FTD; astrocytes; clinical translation; disease modeling; microglia; motor neurons: cortical neurons; neurodegenerative diseases; pluripotent stem cells.