Studies performed in a murine model of MPS IIIA (a neurodegenerative LSD) have demonstrated the therapeutic efficacy of a chimeric sulphamidase engineered to increase its bioavailability by adding the signal peptide (sp) from the iduronate-2-sulphatase (IDS) and the BBB-binding domain (BD) from the Apolipoprotein B (ApoB) (Sorrentino et al., 2013, 2019). The gene discussed is APOB; the disease is mucopolysaccharidosis type 3A.