Unlike the examples thus far discussed, other disorders of single phenotype are not as attractive as targets for neuronal replacement-directed therapy, due to their multicentric pathology, their non-migratory replacement cells, or both. The motor neuronopathies, such as amyotrophic lateral sclerosis and spinal muscular atrophy, are such problematic cases. Spinal motor neurons may be readily generated and purified from hESC and hiPSC cells (Davis-Dusenbery et al., 2014; Karumbayaram et al., 2009; Li et al., 2005; Roy et al., 2005; Wichterle et al., 2002), and yet their clinical utility is limited both by the multi-segmental nature of motor neuron loss in these diseases, and by our limited ability to direct long-distance axonal regrowth and target-specific innervation. As a result, the challenge of designing a cell replacement strategy appropriate for treating a whole-neuraxis multicentric neuronal disorder, even one limited to a single phenotype, has proven daunting.
