Neuronal population models reveal specific linear conductance controllers sufficient to rescue preclinical disease phenotypes.

ABSTRACT: Preclinical drug candidates are screened for their ability to ameliorate in vitro neuronal electrophysiology, and go/no-go decisions progress drugs to clinical trials based on population means across cells and animals. However, these measures do not mitigate clinical endpoint risk. Population-based modeling captures variability across multiple electrophysiological measures from healthy, disease, and drug phenotypes. We pursued optimizing therapeutic targets by identifying coherent sets of ion channel target modulations for recovering heterogeneous wild-type (WT) population excitability profiles from a heterogeneous Huntington's disease (HD) population. Our approach combines mechanistic simulations with population modeling of striatal neurons using evolutionary optimization algorithm

SUBMITTER: Allam SL 

PROVIDER: S-EPMC8577087 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature