Drug attrition rates remain high, with 90% of drugs tested in Phase I trials failing to reach the market. This is even more pronounced for central nervous system (CNS) targeting drugs [1]. One major reason for this is the use of inappropriate preclinical models, which fail to predict successfully the outcome of clinical trials in terms of efficacy and toxicity.
However, induced pluripotent stem cells (iPSCs) and iPSC-derived 3D models offer potential solutions. iPSC-derived 3D neurospheres can be generated from human cells and better recapitulate the biology, morphology and molecular dynamics observed in human in vivo. Additionally, these models can be developed from patient derived iPSC, thus increasing the relevance and predictability of the model.