#$%^&*AU2020200250A120200206.pdf#####ABSTRACT Provided herein are methods and compositions for treating a subject suffering from an enzyme deficiency in the central nervous system (CNS). The bifunctional fusion antibodies provided herein comprise an antibody to an endogenous blood brain barrier (BBB) receptor and an enzyme deficient in mucopolysaccharidosis III (MPS-III). The fusion antibodies provided herein comprise Nsulfoglucosamine sulfohydrolase (SGSH), alpha-N-acetylgulcosaminidase (NAGLU), heparin-alphaglucosaminide N-acetyltransferase (HGSNAT), or N-acetylglucosamine-6-sulfatase (GNS). The methods of treating an enzyme deficiency in the CNS comprise systemic administration of a fusion antibody provided herein. 12024450_1 (GHMatters) P102029.AU.112/14 Figure 12 2 HIRMAb EC50 = 28.8 ±3.2 ng/mL (0. 19 ±0.02 nM) 1.5 A4 0 5 HIRMAb-SGSH EC50 = 106.8 ±16.6 ng/mL (0.33 ±0.05 nM) 0.5 0 0 1000 2000 3000 ng/mL
