To enable fast and confident selection of effective therapies for ALS we develop specific and robust phenotypic assays to study protein mis-localization and aggregation with human iPSC-derived in vitro models.
In this study, we show our iPSC-based platform with miniaturized assays using human iPSC-derived motor neurons to study the effect of new therapeutics in recognized ALS phenotypes:
• Mis-localization of TDP-43 to the cytoplasm
• Aggregation of TDP-43
• Reduction of STMN2 protein levels
• Mis-splicing of STMN2
• Altered electrophysiological properties
• Neurofilament-L secretion
Additionally, this ALS in vitro model was successfully transduced and, when treated with a gene therapy candidate, reduction of TDP-43 aggregation was detected.
Using this platform you can validate your therapeutics, but more importantly, progress with the subset of therapeutics that offer higher confidence for clinical success.