Lee Rubin, from Harvard University, discussed the challenges and successes his laboratory has encountered, in the academic setting, while establishing hiPSC-based high-throughput drug screening for SMA. Given that there are three types of SMA, fatal within the first year of life (type 1), by the teenage years (type 2), and characterized by chronic immobility (type 3), Lee asked whether SMA is in fact one disease or three. To determine why motor neurons from some SMA patients are more sensitive than others, he generated hiPSCs from patients with all three types of SMA, observing that SMA iPSCs have an increased propensity to generate NPCs and a slightly decreased propensity to yield endoderm, consistent with clinical observations that children with SMA have other defects, particularly in endodermal and cardiac tissues. Compared to controls, SMA motor neurons show increased cell death, apoptotic station, reduced neuronal outgrowth, and decreased neuronal firing (SMA3 > SMA2 > SMA1), and regardless of diagnosis, non-motor neurons do not die. Lee conducted three high-throughput screens for compounds to prevent cell death in SMA (ES-derived motor neurons from SMN-deficient mice,
