Validation of ALS-relevant phenotypes in precision reprogrammed iPSC-derived glutamatergic Neurons containing a TDP-43 M337V mutation.

In this poster, Charles River Laboratories assessed whether ioGlutamatergic Neurons TDP-43 M337V from bit.bio was a relevant translational model for vitro drug discovery for ALS. The disease model consists of induced pluripotent stem cell (iPSC)-derived glutamatergic neurons developed by bit.bio, generated using opti-ox precision cellular reprogramming, and CRISPR-edited to contain the TDP-43 M337V mutation seen in rare genetic forms of ALS. This poster shows data from experiments analysing TDP-43 mislocalisation and phosphorylation, and STMN-2 mis-splicing in the presence and absence of MG-132, a proteasomal inhibitor. 

In this poster, you will explore:

• How ioGlutamatergic Neurons TDP-43 M337V were assessed for their relevance as an in vitro ALS disease model.
• How robust assays were established for assessing TDP-43 mislocalisation and phosphorylation, and STMN-2 mis-splicing in this disease model.
• How ioGlutamatergic Neurons TDP-43 M337V show significantly increased TDP-43 mislocalisation and phosphorylation.
• How ioGlutamatergic Neurons TDP-43 M337V show significantly increased STMN-2 mis-splicing
• How these results were confirmed in the presence of an isogenic control, also developed by bit.bio.