Burkhardt et al. performed disease modeling and drug screening using sporadic ALS patient-derived iPSCs125. The authors identified de novo aggregation of TAR DNA-binding protein 43 (TDP-43) in motor neurons of sporadic ALS patients, using TDP-43 aggregation as readout for a high-content drug screen to identify compounds that reduce TDP-43 aggregation125. The same research team also made effective use of patient-derived iPSC model of Alzheimer’s disease126. The authors identified a disease-relevant protein, extracellular tau (eTau), in the conditioned medium of cortical neurons derived from the iPSCs of an Alzheimer’s disease patient, generating a therapeutic antibody against eTau126. This disease-relevant protein would not have been discovered without using the human iPSC model. eTau causes neuronal hyperactivity and increases amyloid beta (Aβ) production. Using human iPSC models as a tool to identify disease-relevant targets could be a critical component for future drug development. Naryshkin et al.127 found that an SMA patient-derived iPSC model could be used to validate human- and disease-specific drug responsiveness after initial screening using a HEK293 cell line127. These compounds were then validated in patient-specific fibroblasts, and in motor neurons
