In this work we characterize the effects of mutant ataxin-3 silencing on MJD-associated motor behavior and neuropathological abnormalities in a pre-symptomatic cerebellar mouse model by co-injecting lentiviral vectors encoding for the silencing short hairpins RNAs and vectors encoding for mutant ataxin-3. Here, ATXN3 is linked to Machado-Joseph disease.