scholarly journals Recombinant human iduronate-2-sulphatase: correction of mucopolysaccharidosis-type II fibroblasts and characterization of the purified enzyme

1993 ◽  
Vol 289 (1) ◽  
pp. 241-246 ◽  
Author(s):  
J Bielicki ◽  
J J Hopwood ◽  
P J Wilson ◽  
D S Anson
Keyword(s):  
Cell Line ◽  
Heparan Sulphate ◽  
Chinese Hamster ◽  
Chain Elongation ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Ph Optimum ◽  
Enzyme Replacement ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-chromosome-linked recessive lysosomal storage disorder that results from a deficiency of iduronate-2-sulphatase (12S). Patients with MPS II store and excrete large amounts of partially degraded heparan sulphate and dermatan sulphate. In order to evaluate enzyme-replacement therapy for MPS II we have expressed a chimaeric I2S cDNA in CHO (Chinese-hamster ovary)-K1 cells utilizing a plasmid vector that places the cDNA under the transcriptional control of the human polypeptide-chain-elongation factor-1 alpha gene promoter. A clonal cell line that accumulated recombinant I2S at greater than 10 mg/ml in conditioned medium was identified. Enzyme secreted from this cell line grown in the presence of NH4Cl was shown to be endocytosed into MPS II fibroblasts via the mannose 6-phosphate receptor and localized to the lysosomal compartment, resulting in correction of the storage phenotype of these cells. Milligram quantities of the recombinant I2S were purified, and the enzyme was shown to have a pH optimum and kinetic parameters similar to those for the mature form of I2S purified from human liver. The recombinant I2S had a molecular mass of approx. 90 kDa; this was reduced to 60 kDa by endoglycosidase treatment.

scholarly journals The Value of Case Reports in Systematic Reviews from Rare Diseases. The Example of Enzyme Replacement Therapy (ERT) in Patients with Mucopolysaccharidosis Type II (MPS-II)

2020 ◽  
Vol 17 (18) ◽  
pp. 6590
Author(s):  
Miguel Sampayo-Cordero ◽  
Bernat Miguel-Huguet ◽  
Andrea Malfettone ◽  
José Manuel Pérez-García ◽  
Antonio Llombart-Cussac ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Systematic Reviews ◽  
Rare Diseases ◽  
Clinical Studies ◽  
Case Reports ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Mps Ii

Background: Case reports are usually excluded from systematic reviews. Patients with rare diseases are more dependent on novel individualized strategies than patients with common diseases. We reviewed and summarized the novelties reported by case reports in mucopolysaccharidosis type II (MPS-II) patients treated with enzyme replacement therapy (ERT). Methods: We selected the case reports included in a previous meta-analysis of patients with MPS-II treated with ERT. Later clinical studies evaluating the same topic of those case reports were reported. Our primary aim was to summarize novelties reported in previous case reports. Secondary objectives analyzed the number of novelties evaluated in subsequent clinical studies and the time elapsed between the publication of the case report to the publication of the clinical study. Results: We identified 11 innovative proposals in case reports that had not been previously considered in clinical studies. Only two (18.2%) were analyzed in subsequent nonrandomized cohort studies. The other nine novelties (81.8%) were analyzed in later case reports (five) or were not included in ulterior studies (four) after more than five years from their first publication. Conclusions: Case reports should be included in systematic reviews of rare disease to obtain a comprehensive summary of the state of research and offer valuable information for healthcare practitioners.

scholarly journals Newborn Screening for Mucopolysaccharidosis Type II in Illinois: An Update

2020 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Barbara K. Burton ◽  
Rachel Hickey ◽  
Lauren Hitchins
Keyword(s):  
Newborn Screening ◽  
Early Years ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Effective Treatment Option ◽  
Positive Screen ◽  
Enzyme Replacement ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, progressive multisystemic lysosomal storage disorder with significant morbidity and premature mortality. Infants with MPS II develop signs and symptoms of the disorder in the early years of life, yet diagnostic delays are very common. Enzyme replacement therapy is an effective treatment option. It has been shown to prolong survival and improve or stabilize many somatic manifestations of the disorder. Our initial experience with newborn screening in 162,000 infants was previously reported. Here, we update that experience with the findings in 339,269 infants. Measurement of iduronate-2-sulfatase (I2S) activity was performed on dried blood spot samples submitted for other newborn screening disorders. A positive screen was defined as I2S activity less than or equal to 10% of the daily median. In this series, 28 infants had a positive screening test result, and four other infants had a borderline result. Three positive diagnoses of MPS II were established, and 25 were diagnosed as having I2S pseudodeficiency. The natural history and the clinical features of MPS II make it an ideal target for newborn screening. Newborn screening was effective in identifying affected infants in our population with an acceptable rate of false positive results.

scholarly journals Gene Therapy for Mucopolysaccharidosis Type II—A Review of the Current Possibilities

2021 ◽  
Vol 22 (11) ◽  
pp. 5490
Author(s):  
Paweł Zapolnik ◽  
Antoni Pyrkosz
Keyword(s):  
Gene Therapy ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Target Cells ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Cellular Models ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder based on a mutation in the IDS gene that encodes iduronate 2-sulphatase. As a result, there is an accumulation of glycosaminoglycans—heparan sulphate and dermatan sulphate—in almost all body tissues, which leads to their dysfunction. Currently, the primary treatment is enzyme replacement therapy, which improves the course of the disease by reducing somatic symptoms, including hepatomegaly and splenomegaly. The enzyme, however, does not cross the blood–brain barrier, and no improvement in the function of the central nervous system has been observed in patients with the severe form of the disease. An alternative method of treatment that solves typical problems of enzyme replacement therapy is gene therapy, i.e., delivery of the correct gene to target cells through an appropriate vector. Much progress has been made in applying gene therapy for MPS II, from cellular models to human clinical trials. In this article, we briefly present the history and basics of gene therapy and discuss the current state of knowledge about the methods of this therapy in mucopolysaccharidosis type II.

scholarly journals Allergic Reactions at Enzyme Replacement Therapy in Children with Mucopolysaccharidosis Type II

2021 ◽  
Author(s):  
Julia G. Levina ◽  
Nato D. Vashakmadze ◽  
Leyla S. Namazova-Baranova ◽  
Elena A. Vishneva ◽  
Natalia V. Zhurkova ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Hunter Syndrome ◽  
Hereditary Disease ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Recombinant Enzymes ◽  
Enzyme Replacement ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is rare hereditary disease caused by changes in the IDS gene and associated deficiency of lysosomal enzyme iduronate-2-sulfatase (I2S). The main treatment scheme for children with MPS II is enzyme replacement therapy (ERT) with recombinant human I2S. The major issue of ERT is development of allergic (sometimes up to severe anaphylaxis) reactions to recombinant enzymes. The article covers features of infusion-related reactions to ERT, it describes pathogenesis, diagnostic criteria management algorithm of anaphylaxis. Whereas, there is the need of further studies on allergic infusion-related reactions to ERT in children.

scholarly journals Enzyme Replacement Therapy with Idursulfase in Patients with Mucopolysaccharidosis Type II: Literature Review

2021 ◽  
Author(s):  
Nato D. Vashakmadze ◽  
Natalya V. Zhurkova ◽  
Olga B. Gordeeva ◽  
Elena V. Komarova ◽  
Tatyana E. Privalova ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
The Body ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Upper Respiratory Tract ◽  
Mucopolysaccharidosis Type Ii ◽  
Central Nervous System Damage ◽  
Enzyme Replacement ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is X-linked hereditary disease from the group of lysosomal storage disease. Its prevalence is 3–7 cases per 1 million live-born boys. MPS II occurs due to the deficiency of iduronate-2-sulfatase enzyme because of pathological changes in the structure of the IDS gene. Enzyme deficiency leads to the accumulation of glycosaminoglycans (GAGs), dermatan sulfate and heparan sulfate, in lysosomes. This leads to the damage of various organs and systems in the body with further development of clinical picture of the disease: coarse face, recurrent infections of upper respiratory tract, hearing loss up to deafness, cardiovascular and respiratory systems pathologies, hepatosplenomegaly, musculoskeletal system abnormalities, low growth, central nervous system damage. Enzyme replacement therapy with idursulfase, that was introduced in clinical practice 15 years ago, has significantly changed the quality of life of these patients. Idursulfase is purified form of natural lysosomal enzyme iduronate-2-sulfatase obtained via human cell line. Exogenous enzyme entry promotes GAGs catabolism in cells. This article provides outcomes analysis of foreign and Russian studies on the efficacy and safety of this medication, and its effect on MPS II patients survivability.

scholarly journals A review of the clinical outcomes in idursulfase-treated and untreated Filipino patients with mucopolysaccharidosis type II: data from the local lysosomal storage disease registry

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Marie Julianne C. Racoma ◽  
Maria Kristina Karizza B. Calibag ◽  
Cynthia P. Cordero ◽  
Mary Ann R. Abacan ◽  
Mary Anne D. Chiong
Keyword(s):  
Adverse Events ◽  
Storage Disease ◽  
Joint Mobility ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Respiratory Involvement

Abstract Background Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycan (GAG) accumulation, caused by a deficiency of iduronate-2-sulfatase (I2S). Enzyme replacement therapy (ERT) with recombinant idursulfase (IDS), the standard of care, was started in the Philippines in 2017. This study reviewed the clinical outcomes in idursulfase-treated and untreated Filipino MPS II patients who were included in the local Lysosomal Storage Disease (LSD) registry of the Institute of Human Genetics-National Institutes of Health (IHG-NIH) from January 1999 to December 2019. Methods A retrospective audit of records of MPS II patients listed in the registry was done. Qualified patients were divided into two cohorts: idursulfase-treated group (patients on enzyme replacement therapy, ERT, for ≥ 6 months) and untreated group. Baseline characteristics, including demographic data, biochemical results, neurocognitive classification, respiratory involvement, mortality, and adverse events, were recorded. Height, weight, cardiac pathology, liver and spleen sizes, six-minute walking test (6MWT), joint mobility, were determined at baseline and at year 1 and 2 of follow up. Results Forty male patients were included in this review, with only 8 receiving ERT since 2017. The mean age at diagnosis was 6.99 years (SD 4.15; 0.75–20) and mean age at start of ERT was 14.03 years (SD 7.1; 4–21.5), more delayed than previous reports. Eighty percent have early progressive phenotype which was higher than reported average. The early growth pattern differed in our Filipino cohort, but was followed by the expected slowed growth in later years. Improvements in the following endpoints were observed in the treated cohort: height and weight, cardiac disease, liver and spleen sizes, and joint mobility. There were also positive effects on respiratory involvement and mortality rate. Adverse events were consistent with previous reports. Conclusions ERT is generally well tolerated and effective in reducing GAG storage and improving clinical endpoints among our Filipino MPS II patients. In untreated patients, typical disease progression was observed.

scholarly journals A Review Of The Clinical Outcomes In Idursulfase-Treated And Untreated Filipino Patients With Mucopolysaccharidosis Type II: Data From The Local Lysosomal Storage Disease Registry

2020 ◽  
Author(s):  
Marie Julianne Castillo Racoma ◽  
Maria Kristina Karizza B. Calibag ◽  
Mary Anne D. Chiong ◽  
Mary Ann R. Abacan ◽  
Cynthia Cordero
Keyword(s):  
Adverse Events ◽  
Storage Disease ◽  
Joint Mobility ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Respiratory Involvement

Abstract Background: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycan (GAG) accumulation, caused by a deficiency of iduronate-2-sulfatase (I2S). Enzyme replacement therapy (ERT) with recombinant I2S, the standard of care, was started in the Philippines in 2017. This study reviewed the clinical outcomes in idursulfase-treated and untreated Filipino MPS II patients who were included in the local Lysosomal Storage Disease (LSD) registry of the Institute of Human Genetics-National Institutes of Health (IHG-NIH) from January 1999 to December 2019.Methods: A retrospective audit of records of MPS II patients listed in the registry was done. Qualified patients were divided into two cohorts: idursulfase-treated group (patients on enzyme replacement therapy, ERT, for >6 months) and untreated group. Baseline characteristics, including demographic data, biochemical results, neurocognitive classification, respiratory involvement, mortality, and adverse events, were recorded. Height, weight, cardiac pathology, liver and spleen sizes, six-minute walk test (6MWT), joint mobility, were determined at baseline and at year 1 and 2 of follow up.Results: Forty male patients were included in this review, with 8 receiving ERT since 2017. The mean age at diagnosis was 6.99 years (SD 4.15; 0.75-20) and mean age at start of ERT was 14.03 years (SD 7.1; 4-21.5), more delayed than previous reports. Eighty percent have early progressive phenotype which was higher than reported average. The early growth pattern differed in our Filipino cohort, but was followed by the expected slowed growth in later years. Improvements in the following endpoints were observed in the treated cohort: height and weight, cardiac disease, liver and spleen sizes, and joint mobility. There were also positive effects on respiratory involvement and mortality rate. Adverse events were consistent with previous reports.Conclusions: ERT is generally well tolerated and effective in reducing GAG storage and improving clinical endpoints among our Filipino MPS II patients. In untreated patients, typical disease progression was observed.

scholarly journals Autophagy in the Central Nervous System and Effects of Chloroquine in Mucopolysaccharidosis Type II Mice

2019 ◽  
Vol 20 (23) ◽  
pp. 5829 ◽  
Author(s):  
Mitsuyo Maeda ◽  
Toshiyuki Seto ◽  
Chiho Kadono ◽  
Hideto Morimoto ◽  
Sachiho Kida ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Neuronal Degeneration ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II) is a rare lysosomal storage disease (LSD) involving a genetic error in iduronic acid-2-sulfatase (IDS) metabolism that leads to accumulation of glycosaminoglycans within intracellular lysosomes. The primary treatment for MPS II, enzyme replacement therapy, is not effective for central nervous system (CNS) symptoms, such as intellectual disability, because the drugs do not cross the blood–brain barrier. Recently, autophagy has been associated with LSDs. In this study, we examined the morphologic relationship between neuronal damage and autophagy in IDS knockout mice using antibodies against subunit c of mitochondrial adenosine triphosphate (ATP) synthetase and p62. Immunohistological changes suggesting autophagy, such as vacuolation, were observed in neurons, microglia, and pericytes throughout the CNS, and the numbers increased over postnatal development. Oral administration of chloroquine, which inhibits autophagy, did not suppress damage to microglia and pericytes, but greatly reduced neuronal vacuolation and eliminated neuronal cells with abnormal inclusions. Thus, decreasing autophagy appears to prevent neuronal degeneration. These results suggest that an autophagy modulator could be used in addition to conventional enzyme replacement therapy to preserve the CNS in patients with MPS II.

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