A Small Molecule Screen in Stem-Cell-Derived Motor Neurons Identifies a Kinase Inhibitor as a Candidate Therapeutic for ALS

摘要: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, characterized by motor neuron (MN) death, for which there are no truly effective treatments. Here, we describe new small molecule survival screen carried out using MNs from both wild-type and mutant SOD1 mouse embryonic stem cells. Among the hits found, kenpaullone had particularly impressive ability to prolong healthy of types that can be attributed its dual inhibition GSK-3 HGK kinases. Furthermore, also strongly improved human derived ALS-patient-induced pluripotent cells was more active than either two compounds, olesoxime dexpramipexole, recently failed in ALS clinical trials. Our studies demonstrate value cell approach drug discovery point paradigm identification preclinical testing future therapeutics.