Dorsal root ganglion (DRG) toxicity is a significant concern in drug development, especially for therapies targeting the nervous system. Existing in vitro models lack the necessary optimization to predict DRG toxicity accurately. This study aimed to develop and validate a rat DRG-microglia co-culture model to address this gap.
The rat DRG-microglia co-culture model was optimized and tested using inflammatory agents and known neurotoxic compounds. Treatments included LPS + IFNγ to induce inflammation, Paclitaxel to assess neurite disorganization, and Colchicine to evaluate microglial activation and toxicity. Exploratory small molecules, oligonucleotides, and AAVs were also tested for predictive validation.
The rat DRG-microglia co-culture model effectively predicts neurotoxicity across small molecules, oligonucleotides, and AAVs. This innovative model enhances drug safety assessments, providing a powerful tool for preclinical evaluation of therapies targeting the nervous system.
