Alpha-N-acetylglucosaminidase (NAGLU) (NAGLU)

Alpha-N-acetylglucosaminidase (NAGLU) is a lysosomal hydrolase essential for the degradation of heparan sulfate, a glycosaminoglycan (GAG) involved in cell signaling and structural integrity (UniProt P54802). Deficiency of this enzyme, caused by mutations in the NAGLU gene, leads to Mucopolysaccharidosis type IIIB (MPS IIIB), also known as Sanfilippo syndrome type B (OMIM 252920). This condition is characterized by the pathological accumulation of partially degraded heparan sulfate within lysosomes, particularly in the central nervous system, leading to progressive neurodegeneration, cognitive decline, and behavioral issues (PubMed 31141617). Therapeutic strategies primarily involve enzyme replacement therapy (ERT), such as Tralesinidase alfa, which aims to provide functional NAGLU to lysosomes, or gene therapies like ABO-101 designed to restore endogenous enzyme production (PubMed 28813360). A significant challenge in drug development for this target is ensuring the enzyme reaches the brain in sufficient quantities, often requiring direct intrathecal or intracerebroventricular administration. Monitoring efficacy typically involves measuring heparan sulfate levels in the cerebrospinal fluid or urine, alongside assessing NAGLU enzyme activity (PubMed 23902209).

Other names

N-acetyl-alpha-D-glucosaminidaseNAGAlpha-N-acetyl-D-glucosaminidaseSanfilippo B protein

Enzyme replacement therapy (ERT) to degrade accumulated heparan sulfate and gene therapy to restore functional NAGLU expression.