Iduronate-2-sulfatase (IDS) (IDS)

Iduronate-2-sulfatase (IDS) is a lysosomal enzyme essential for the degradation of glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate [1]. It functions by removing the 2-sulfate group from L-iduronate-2-sulfate residues within these complex carbohydrates. Mutations in the IDS gene lead to a deficiency of this enzyme, resulting in Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, a progressive X-linked lysosomal storage disorder [2]. The resulting systemic accumulation of undegraded GAGs causes multi-organ dysfunction, including skeletal abnormalities, hepatosplenomegaly, and cardiovascular complications, with severe phenotypes exhibiting neurocognitive decline [2]. Therapeutic interventions focus on restoring IDS activity through enzyme replacement therapy (ERT) or gene therapy [3]. Modern gene therapy approaches, such as those utilizing AAV9 vectors (e.g., RGX-121), aim to deliver the IDS transgene across the blood-brain barrier to address the neurological manifestations of the disease by providing a continuous source of the functional enzyme [3, 4]. This approach seeks to overcome the limitations of traditional ERT, which does not effectively cross the blood-brain barrier to treat CNS symptoms [4]. Sources: [1] UniProt P22304; [2] NIH GARD Hunter Syndrome; [3] REGENXBIO RGX-121 Program; [4] Muenzer J, et al. (2021) Molecular Genetics and Metabolism.

Other names

I2SIduronate 2-sulfataseAlpha-L-iduronate sulfate sulfataseIduronate-2-sulphataseMPS2

Restoration of lysosomal enzymatic activity to catalyze the hydrolysis of 2-sulfate groups from iduronate residues in glycosaminoglycans, preventing toxic cellular accumulation.