Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder that leads to the loss of upper and lower motor neurons. It has a genetic background in which 10% of the cases have a positive family history of mutations in the superoxide dismutase 1 (SOD1) gene which is associated with the most common familial form of ALS. In addition, there is an estimate of 30 genes directly linked to the pathophysiology of the disease, including TARDBP, FUS, OPTN, VCP, UBQLN2, C9ORF72, PFN1…etc., and over 120 other genes indirectly associated with ALS (Abel et al., 2012). Generation of iPSCs from patients with ALS and their differentiation into motor neurons was first reported in 2008 (Dimos et al., 2008; Table 3). In his study, Dimos et al. (2008) used skin fibroblasts collected from an 82-year-old patient diagnosed with familial ALS to produce patient-specific iPSCs. These cells were subsequently plated in suspension culture to form EBs, then treated with RA and recombinant SHH to persuade neural differentiation. When these differentiated EBs were plated on a laminin-coated surface and allowed to mature for 7–15 days, they started forming neuron-like outgrowths that stained positive for TUJ1, confirming their neuronal nature.
