As shown by AstraZeneca in nature reviews*, one third of the safety failures is linked to CNS toxicity during the clinical trials of drugs .
* Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN (2014) Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-imensional framework. Nat Rev Drug Discov. 13(6):419-31.
The potential neurotoxicity of any drug going through the blood brain barrier (BBB) needs to be checked and if possible at the early stage of the research process. This assay can be performed by cell imaging in HCA/HCS.
To learn more on this assay, see also our poster presented in different congress.
Neurotoxicity assay will be performed by treated neuronal cells during 48h with the tested compounds. Staining has been performed with hoechst, beta III tubulin (neurites marker) and mitotracker (mitochondrial activity marker):
Morphology changes appeared and neurite connection can also decreased without neuronal cell death.
Cells can also undergo autophagy (process well described in Alzheimer desease) , which can be followed through Lc3B analysis. Example below on neuronal cells: