Methods and compositions for increasing the activity of hexosaminidase A, acid sphingomyelinase and palmitoyl-protein thioesterase 1 in the CNS.

摘要

Provided herein are methods and compositions for treating subjects with enzyme deficiencies in the central nervous system (CNS). The bifunctional fusion antibodies provided herein are antibodies to the endogenous blood-brain barrier (BBB) receptor as well as lysosomal enzymes, hexosaminidase A (HEXA), acid sphingomyelinase (ASM) and palmitoyl-protein thioesterase. It may contain enzymes that are deficient in Tay-Sachs disease (TSD), Niemann-Pick disease (NPD) or neurocereloid lipofustin deposition disease 1 (NCL1) due to a mutation in 1 (PPT1). The fusion antibody provided herein may include HEXA, ASM and PPT1. Methods of treating enzyme deficiencies in the CNS may include systemic administration of the fusion antibodies provided herein.