Abstract
CNS toxicity is one of the primary reasons for discontinuing the development of new pharmaceuticals. Particularly, risks such as seizure might lead to development termination or dose restrictions during clinical trials, acting as significant hurdles. Neurotoxicity assessment has traditionally relied on methods like modified Irwin’s method and FOB, along with in vivo evaluation systems specific to individual neurological symptoms. However, practical in vitro evaluation options have been lacking. Nowadays, human iPSC-derived neural cells have emerged as in vitro experimental materials alongside rat neuronal primary cultures, breaking down species barriers and offering new possibilities for drug evaluation. Additionally, advancements in measurement devices, such as MEA and imaging tools, have demonstrated the usefulness of novel evaluation platforms worldwide. Furthermore, there are ongoing efforts to construct neural functional evaluation systems that combine simplicity and throughput using techniques like Ca-transient assays with fluorescent sensors. I will introduce experiments conducted by the CSAHi Ca-transient team. Beyond the conventional in vivo neurotoxicity assessments, I will comprehensively discuss other potential experimental systems, including Secondary Pharmacology and the utilization of EEG, considering central nervous system toxicity. Additionally, I will provide information on in vitro evaluation systems for peripheral neurotoxicity. I aim to explore existing possibilities and discuss how to effectively utilize them in the drug development.
