Hunter syndrome is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to the accumulation of glycosaminoglycans (GAGs). Two recombinant enzymes, idursulfase and idursulfase beta are currently available for enzyme replacement therapy for Hunter syndrome. These two enzymes exhibited some differences in various clinical parameters in a recent clinical trial. Regarding the similarities and differences of these enzymes, previous research has characterized their biochemical and physicochemical properties. We compared the in vitro and in vivo efficacy of the two enzymes on patient fibroblasts and mouse model. Two enzymes were taken up into the cell and degraded GAGs accumulated in fibroblasts. In vivo studies of two enzymes revealed similar organ distribution and decreased urinary GAGs excretion. Especially, idursulfase beta exhibited enhanced in vitro efficacy for the lower concentration of treatment, in vivo efficacy in the degradation of tissue GAGs and improvement of bones, and revealed lower anti-drug antibody formation. A biochemical analysis showed that both enzymes show largely a similar glycosylation pattern, but the several peaks were different and quantity of aggregates of idursulfase beta was lower.
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| http://dx.doi.org/10.1038/jhg.2016.133 | DOI Listing |
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Intracerebroventricular enzyme replacement therapy in patients with neuronopathic mucopolysaccharidosis type II: Final report of 5-year results from a Japanese open-label phase 1/2 study.
Mol Genet Metab
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Department of Clinical Genomics, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241, Japan; Division of Medical Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. Electronic address:
Intravenous idursulfase is standard treatment for mucopolysaccharidosis II (MPS II) in Japan. In the interim analysis of this open-label, phase 1/2 study (Center for Clinical Trials, Japan Medical Association: JMA-IIA00350), intracerebroventricular (ICV) idursulfase beta was well tolerated, suppressed cerebrospinal fluid (CSF) heparan sulfate (HS) levels, and stabilized developmental decline over 100 weeks in Japanese children with MPS II. Here, we report the final study results, representing 5 years of ICV idursulfase beta treatment.
View Article and Find Full Text PDFLong-term experience with idursulfase beta (Hunterase) in two adolescent patients with MPS II: A case series.
Mol Genet Metab Rep
September 2023
Department of Genetics, Hospital Kuala Lumpur, Malaysia.
Mucopolysaccharidosis (MPS) type II (Hunter syndrome) is a rare X-linked, recessive, lysosomal storage disorder caused by the deficit of the enzyme iduronate 2-sulfatase (IDS), resulting in accumulation of glycosaminoglycans (GAGs) impairing cellular function in multiple organ systems. Idursulfase (Elaprase, Takeda Pharmaceuticals) and idursulfase beta (Hunterase, GC Biopharma Corp.) are the two currently available enzyme replacement therapies (ERT) for MPS II in Malaysia.
View Article and Find Full Text PDFImpact of ERT and follow-up of 17 patients from the same family with a mild form of MPS II.
Clinics (Sao Paulo)
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Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
Background: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme Iduronate-2- Sulfatase (IDS), leading to progressive accumulation of Glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefits for patients, retarding the natural progression of the disease.
Results: The authors evaluated 17 patients from the same family with a mild form of MPS type II; the proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgical complications shortly after the procedure.
Impact of intracerebroventricular enzyme replacement therapy in patients with neuronopathic mucopolysaccharidosis type II.
Mol Ther Methods Clin Dev
June 2021
Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
This open-label, phase 1/2 study (JMACCT CTR JMA-IIA00350) evaluated the efficacy and safety of intracerebroventricular idursulfase beta in patients with mucopolysaccharidosis II (MPS II). Herein, we report the 100-week results. Six patients with severe MPS II aged 23-65 months were enrolled.
View Article and Find Full Text PDFAnalysis of long-term observations of the large group of Russian patients with Hunter syndrome (mucopolysaccharidosis type II).
BMC Med Genomics
March 2021
Research Centre for Medical Genetics RAN, 1 Moskvorechie St., Moscow, 115522, Russia.
Background: This article presents the results of long-term observations and comparative analysis of genotype-phenotype features in a large group of patients (227 males and one female) with a severe, intermediate and mild form of Hunter syndrome, evaluating the quality and span of their lives, as well as their ability to social adaptation.
Methods: We used electrophoresis of glycosaminoglycans of urine, determination of the activity of lysosomal enzymes in plasma, in dried blood spots according to the generally accepted method and DNA analysis.
Results: The clinical symptomatology of 228 patients with Hunter syndrome was characterized by growth retardation, lesions of the bronchopulmonary, cardiovascular, nervous systems, etc.
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