Selective Silencing of TDP-43 P. G376D Mutation Reverses Key Amyotrophic Lateral Sclerosis-Related Cellular Deficits - PubMed
7 hours ago
- #Amyotrophic Lateral Sclerosis
- #RNA Interference
- #TDP-43
- An allele-specific siRNA designed to selectively silence the mutant TDP-43 G376D allele shows therapeutic promise in ALS by targeting the underlying genetic cause.
- In iPSC-derived motor neurons, the siRNA treatment effectively reduces TDP-43 mislocalization, decreases cytoplasmic aggregation, and lowers oxidative stress.
- The intervention enhances lysosomal function and improves cell viability, directly addressing key pathological phenotypes observed in ALS motor neurons.
- This approach represents a targeted therapy strategy specifically for patients carrying the TDP-43 G376D mutation, potentially offering a pathway to modify disease progression.