N-sulfoglucosamine sulfohydrolase (SGSH) (SGSH)

N-sulfoglucosamine sulfohydrolase (SGSH), commonly referred to as sulfamidase, is a critical lysosomal enzyme involved in the stepwise degradation of the glycosaminoglycan heparan sulfate (Source: UniProt P51688). It specifically functions as a hydrolase that removes sulfate groups from N-sulfated glucosamine residues. A genetic deficiency in SGSH results in Mucopolysaccharidosis type IIIA (MPS IIIA), or Sanfilippo syndrome type A, a lysosomal storage disorder characterized by the accumulation of undegraded heparan sulfate in tissues, most notably the brain (Source: NIH GARD). This accumulation triggers a cascade of neuroinflammation and cellular dysfunction, leading to severe and progressive neurodegeneration, intellectual disability, and loss of motor function. The target is currently the focus of advanced gene therapy clinical trials, such as those utilizing AAV9-mediated delivery (e.g., ABO-102), which aim to provide a functional copy of the SGSH gene to restore enzyme production (Source: PubMed 31653511). By re-establishing SGSH activity, these therapies seek to clear accumulated heparan sulfate and halt or reverse the progression of neurological symptoms. Monitoring efficacy typically involves measuring heparan sulfate levels in the cerebrospinal fluid and urine, while safety concerns include potential immune reactions to the viral vector and liver toxicity. Successful delivery and expression of SGSH represent a primary therapeutic goal for addressing the unmet medical need in Sanfilippo syndrome type A.

Other names

SulfamidaseHeparan sulfate sulfataseHSSSFMDN-sulfoglucosamine sulfohydrolase

Gene replacement therapy to restore functional SGSH enzyme activity for heparan sulfate degradation.