High-throughput screening of ALS patient iPSC-derived spinal motor neurons identifies novel compounds that increase neurofilament light chain expression - PubMed
5 hours ago
- #ALS
- #iPSC
- #drug discovery
- ALS is a fatal neurodegenerative disease affecting motor neurons, with pathology including protein inclusions and neurofilament aggregates.
- Current ALS treatments offer limited survival benefits, underscoring the need for new therapies.
- Researchers developed a high-throughput screening system using ALS patient-derived iPSCs differentiated into spinal motor neurons.
- Over 6,000 compounds were screened, identifying a novel compound that increases neurofilament light chain (NF-L) expression by more than 50%.
- The initial compound inhibited TGF-β signaling, leading to optimization efforts.
- A second compound was found that does not affect TGF-β signaling and shows better performance in drug metabolism and pharmacokinetics assays.
- The study demonstrates the value of iPSC-derived neurons in disease modeling and drug discovery.