Description:
- Novel ASO therapeutic targeting CCDC146, a newly identified driver of motor neuron degeneration in ALS
- Demonstrated efficacy across both sporadic and familial ALS models, supporting broad patient applicability
- Improves motor function, neuronal survival, and lifespan in preclinical ALS models
Abstract
USC researchers have developed a targeted antisense oligonucleotide (ASO) that suppresses CCDC146, a gene identified as a key driver of motor neuron loss in ALS. In patient-derived iPSC neurons, CCDC146 ASOs improved cell survival across both sporadic and familial ALS backgrounds. In ALS mouse models, treatment enhanced motor function, reduced neurodegeneration, and extended survival. This gene-targeting approach is effective regardless of genetic subtype, making it broadly applicable to the heterogeneous ALS population.
Benefit
- Demonstrated efficacy in diverse ALS genetic backgrounds
- Improves motor function and survival in ALS mouse models
- Improves cell survival in both sporadic and familial ALS backgrounds
Publications
Antisense oligonucleotide depletion of CCDC146 is a broad-spectrum therapeutic strategy for ALS, medRxiv, August 19. 2025.
Other
- Available for Licensing and Sponsored Research Agreements
- Validated in ALS patient-derived iPSC neurons and hTDP43 mouse models