Induced pluripotent stem cells for modeling of spinal muscular atrophy

Abstract Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by the disruption of the survival of motor neuron-1 (SMN1) gene, which leads to motor neuron cell death, skeletal muscle wasting, and premature death. Encouragingly, therapies have been developed in recent years providing the first forms of treatment for SMA patients. However, further research into the disease etiology, onset of disease progression, and the impact of wide-spread SMN disruption across different cell types is still needed to better define disease mechanisms and novel therapeutic targets. Induced pluripotent stem cells (iPSCs) provide a clinically relevant, ethical, and highly scalable cell source for use in human in vitro model systems for multiple applications. In this book chapter, we highlight the progress that has been made using SMA iPSC-derived culture systems to investigate motor neuron vulnerability, to characterize dysfunction in other disease relevant cells, for therapeutic testing and for potential use in cell transplantation therapies. We will also comment on the advances in iPSC technology, such as organoid and assembloid culture systems, and how these can facilitate novel discoveries in SMA disease modeling and therapy development for future research.