In response, cell-based treatment approaches for ALS and other neurodegenerative disorders have begun to shift away from neuronal replacement, towards the delivery of astrocytes, with the goal of correcting underlying glial metabolic deficiencies that may contribute to disease progression in ALS. If successful, one may envision a rapid transition to the use of hiPSC-derived glia for this and related disorders in which neurons may prove the paracrine victims of glial dysfunction. In that respect, a number of recent reports have highlighted the causal contribution of glial cells to the pathogenesis of ALS (Di Giorgio et al., 2008; Di Giorgio et al., 2007; Meyer et al., 2014; Yamanaka et al., 2008), which has led to a number of trials and trial plans focused on spinal glial addition, whether from transplanted astrocytes or their precursors, the latter including neural stem cells (Feldman et al., 2014; Lunn et al., 2014). These efforts have thus far been limited to the use of human fetal tissue-derived glia, which have yielded acceptable safety profiles but for which therapeutic efficacy remains to be assessed; analogous trials have not yet proceeded to the use of PSC-derived glia.
