Urinary glycosaminoglycans as a potential biomarker for evaluating treatment efficacy in subjects with mucopolysaccharidoses.

ABSTRACT

Accumulations of glycosaminoglycans (GAGs) that result from deficiencies in lysosomal hydrolases are characteristic of mucopolysaccharidoses (MPS). Enzyme replacement therapies (ERTs) are now available for several MPS diseases (MPS I, MPS II, MPS IVA, MPS VI, and MPS VII), but assessment of the efficacy of treatment can be challenging because these are rare, progressive, and highly heterogeneous diseases; because some clinical manifestations may be irreversible if treatment initiation is delayed; and because determining the benefits of a treatment to prevent those manifestations may take prolonged periods of time. In addition to accumulation of GAGs in tissues, elevated urinary GAG (uGAG) levels are evident and are reduced rapidly after initiation of ERT. Studies in MPS animal models and clinical studies in subjects with MPS diseases have revealed correlations between reductions of uGAG levels and clinical effects of ERTs. In this article, we review the growing body of evidence to support the potential for the use of uGAG levels as predictive biomarkers of treatment efficacy.