[MS10-4B-3] The Protective Effects of Edaravone in Generated Spinal Motor Neuron Using iPSCs Derived from a Spinal Muscular Atrophy Patient
[Introduction] Spinal muscular atrophy (SMA) is a genetic disease caused by a deletion or mutation of survival motor neuron 1 gene leading to selective motor neuron loss and skeletal muscle atrophy. While it is shown that reduced levels of survival motor neuron (SMN) protein causes SMA pathology, no effective therapeutic strategies have been established so far. Additionally, it remains unclear why reduced SMN protein level results in selective apoptosis in spinal motor neurons although SMN protein were expressed ubiquitously. In this study, we used induced pluripotent stem cells from an SMA patient (SMA-iPSCs) to address oxidative stress-induced apoptosis in spinal motor neurons and evaluate the therapeutic potential of edaravone, a free radical scavenger.
[Methodology] SMA-iPSCs were differentiated into spinal motor neuron by the same steps described normal embryonic development. To evaluate the effect of edaravone, SMA-iPSCs-derived spinal motor neurons were exposed to 1 µM edaravone for two weeks. Then, SMN protein level, reactive oxygen species (ROS) level, neural elongation, and apoptosis markers were determined.
[Results] Edaravone suppressed the upregulation of intracellular ROS and generation of mitochondrial ROS in SMA-iPSCs-derived spinal motor neurons, We also found that edaravone could increase SMN protein level and improve impaired neural development of SMA-iPSCs-derived spinal motor neurons. Furthermore, edaravone reversed oxidative-stress induced apoptosis.
[Conclusions] Oxidative stress-induced apoptosis might be the therapeutic target of SMA. We show here the potential effect of edaravone for the therapy of SMA.
[Methodology] SMA-iPSCs were differentiated into spinal motor neuron by the same steps described normal embryonic development. To evaluate the effect of edaravone, SMA-iPSCs-derived spinal motor neurons were exposed to 1 µM edaravone for two weeks. Then, SMN protein level, reactive oxygen species (ROS) level, neural elongation, and apoptosis markers were determined.
[Results] Edaravone suppressed the upregulation of intracellular ROS and generation of mitochondrial ROS in SMA-iPSCs-derived spinal motor neurons, We also found that edaravone could increase SMN protein level and improve impaired neural development of SMA-iPSCs-derived spinal motor neurons. Furthermore, edaravone reversed oxidative-stress induced apoptosis.
[Conclusions] Oxidative stress-induced apoptosis might be the therapeutic target of SMA. We show here the potential effect of edaravone for the therapy of SMA.