MSH3 and Huntington disease: TTX-3360, an ASO delivered by intracerebroventricular (ICV) injection, targeting MSH3, a component of the DNA damage response pathway that sits upstream of mHTT to drive disease onset and progression.[128,129] The preclinical data showed that MSH3 knockdown in normal mice and two mouse models of HD was safe and well-tolerated; 50% knockdown of MSH3 with TTX-3360 in HD patient-derived cell lines, and with the tool ASO targeting Msh3 in the HD mouse model, slowed or stopped expansion of mutant HTT repeats.