Transplantation of Neural Progenitor Cells Expressing Glial Cell Line‐Derived Neurotrophic Factor into the Motor Cortex as a Strategy to Treat Amyotrophic Lateral Sclerosis

Early dysfunction of cortical motor neurons may underlie the initiation of amyotrophic lateral sclerosis (ALS). As such, the cortex represents a critical area of ALS research and a promising therapeutic target. In the current study, human cortical‐derived neural progenitor cells engineered to secrete glial cell line‐derived neurotrophic factor (GDNF) were transplanted into the SOD1G93A ALS rat cortex, where they migrated, matured into astrocytes, and released GDNF. This protected motor neurons, delayed disease pathology and extended survival of the animals. These same cells injected into the cortex of cynomolgus macaques survived and showed robust GDNF expression without adverse effects. Together this data suggests that introducing cortical astrocytes releasing GDNF represents a novel promising approach to treating ALS. Stem Cells 2018;36:1122–1131 Human neural progenitor cells engineered to secrete glial cell line‐derived neurotrophic factor were transplanted into the motor cortex of SOD1G93A amyotrophic lateral sclerosis (ALS) rats (A). These cells surround host CTIP2+ corticospinal motor neurons (B), which appear to take up this supportive growth factor (C). This strategy promotes the health of motor neurons (D) and is effective in delaying disease onset (E) and extending survival in this model suggesting that this is a novel promising approach to treating ALS. Scale bar (B) = 25 μm, (C) = 5 mm.