Here, the performance of HexD3 is tested head-to-head against HexA at various stages of disease severity and after onset of symptoms in an SD mouse model engineered to have Hexβ gene knockout and subsequent loss of the β-subunit; this model has been used extensively as the preclinical mouse model for testing therapies for both SD and TSD [11]. Here, HEXB is linked to Tay-Sachs disease.