Suppression of TDP-43 Proteinopathy in Mice by Targeting rad-23

Normally cells continually synthesize new proteins and dispose of old and damaged proteins. In ALS, damaged proteins are not properly eliminated, leading to their accumulation and this compromises cell health. Major therapeutic efforts are underway world-wide to devise new strategies for enhancing elimination of damaged proteins. Several labs have shown that reducing the abundance of a key regulatory protein called RAD23 has a broad action of enhancing elimination of damaged proteins. In a variety of disease models this benefits neuronal healthy and survival. To translate these observations into a human, we will test the efficacy of a therapeutic technology called anti-sense oligonucleotides (ASO). The goal of this project is to determine whether ASO that target the destruction of RAD23 confers benefits on a mouse model of ALS.