Official websites use. Share sensitive information only on official, secure websites. Louis, MO Phone Therapeutic development and monitoring require demonstration of effects on disease phenotype. However, due to the complexity of measuring clinically-relevant effects in rare multisystem diseases, robust biomarkers are essential. For the mucopolysaccharidoses MPS , the measurement of glycosaminoglycan levels is relevant as glycosaminoglycan accumulation is the primary event that occurs due to reduced lysosomal enzyme activity.
Traditional dye-based assays that measure total glycosaminoglycan levels have a high background, due to a normal, baseline glycosaminoglycan content in unaffected individuals. An assay that selectively detects the disease-specific non-reducing ends of heparan sulfate glycosaminoglycans that remain undegraded due to deficiency of a specific enzyme in the catabolic pathway avoids the normal background, increasing sensitivity and specificity.
We evaluated glycosaminoglycan content by dye-based and non-reducing end methods using urine, serum, and cerebrospinal fluid from MPS I human samples before and after treatment with intravenous recombinant human alpha- l -iduronidase. We found that both urine total glycosaminoglycans and serum heparan sulfate derived non-reducing end levels were markedly decreased compared to baseline after 26 weeks and 52 weeks of therapy, with a significantly greater percentage reduction in serum non-reducing end Unexpectedly, we also observed a decrease in non-reducing end levels in cerebrospinal fluid in all five subjects for whom samples were collected mean Results suggest utility of the non-reducing end assay in evaluating a therapeutic response in MPS I.
Keywords: Mucopolysaccharidosis, lysosomal storage disorder, enzyme replacement therapy, Hurler, glycosaminoglycan.
Administered as a weekly infusion, IV rhIDU has been shown to reduce lysosomal glycosaminoglycan storage and improve many clinical symptoms including liver and spleen size, range of motion and functional status measures [ 2 , 3 ].
