scholarly journals HUNTER SYNDROME: FIRST ITALIAN CASE TREATED WITH ENZYME-REPLACEMENT THERAPY. TEN YEARS OF FOLLOW-UP

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
C. De Rose ◽  
R. Angotti ◽  
M. Cioni ◽  
M. Sica ◽  
C. Pellegrino ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Biological Fluids ◽  
Heparan Sulphate ◽  
Hunter Syndrome ◽  
Whole Body ◽  
Neurological Involvement ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
First Case

The Hunter syndrome (Mucopolysaccharidosis II, MPS II) is a severe genetic disease (X-linked recessive). Its incidence is about 0.3-0.71 per 100 000 live births. It is caused by the deficiency in the lysosomal enzyme iduronate-2-sulphatase (I2S), which catalyses the degradation of the glycosaminoglycans (GAG). This leads to a widespread accumulation of the GAG dermatan and heparan sulphate in many organs with a final progressive multi-system disease. The enzyme-replacement therapy (ERT) with idursulfase, a recombinant human I2S enzyme, is now available (since 2006) in many countries. We described the first case treated in Italy with this method. A 13-month-old male arrived to our Clinic and was diagnosed with MPS II. He was treated with ELAPRASE (0.5 mg/kg intravenously administered every week) since 32 months of age. We monitored the urinary GAG content, the patient’s detailed anthropometric (growth, weight, phenotypic aspects of the face, as well as chest, limbs and whole body), joint range of motion and skeletal radiographs, ultrasound studies of liver and spleen volumes, the distance covered in the 6-minute walk test and respiratory symptoms, echocardiography and heart valvulopathies, otorinolaryngological symptoms, audiological examinations, pain, neurological involvement and psychological tests. The patient was treated for 10 years and he is still in treatment. He now presents i) significant reduction in GAG levels in the biological fluids, ii) important improvements in lung function, in the ability of walking, in other visceral organs function and iii) a significant reduction of the liver and spleen volumes. We can conclude that an early diagnosis is fundamental for an efficient therapy of the Hunter syndrome disease. Indeed the treatment of patients with MPS II before the onset of clinical symptoms may significantly improve the quality of life and the survival. The ELAPRASE treatment is a good option for these patients, but not all patients with MPS II may be elected for this type of treatment. An accurate selection is fundamental also based on high cost of medication.

Enzyme replacement therapy in Hunter syndrome (MPS II): A systematic review with narrative synthesis and meta-analysis

2020 ◽  
Vol 129 (2) ◽  
pp. S54
Author(s):  
María José Esteban Giner ◽  
Philip Wikman-Jorgensen ◽  
Ana Lopez-Amorós ◽  
Jorge Peris ◽  
Pedro Jesús Esteve-Atienzar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Meta Analysis ◽  
Hunter Syndrome ◽  
Narrative Synthesis ◽  
Enzyme Replacement ◽  
Mps Ii

scholarly journals Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II: an Integrated Analysis of Preclinical and Clinical Data

2021 ◽  
Author(s):  
Roberto Giugliani ◽  
Ana Maria Martins ◽  
Torayuki Okuyama ◽  
Yoshikatsu Eto ◽  
Norio Sakai ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Hunter Syndrome ◽  
Integrated Analysis ◽  
Mice Model ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Progressive Neurodegeneration ◽  
Cns Effects

Enzyme replacement therapy (ERT) improves the somatic manifestations in mucopolysaccharidoses (MPS))．However, because intravenously administered enzymes cannot cross the blood brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT intend to achieve CNS effects, but the burdens on patients are inimical to long-term multiple administrations. However, after pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in mice model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the hitherto obtained preclinical and clinical evidence associated with this drug, and discusses the preclinical, translational and clinical challenges of evaluating, ameliorating and preventing the neurodegeneration in patients with MPS-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 Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II: An Integrated Analysis of Preclinical and Clinical Data

2021 ◽  
Vol 22 (20) ◽  
pp. 10938
Author(s):  
Roberto Giugliani ◽  
Ana Maria Martins ◽  
Torayuki Okuyama ◽  
Yoshikatsu Eto ◽  
Norio Sakai ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Clinical Evidence ◽  
Hunter Syndrome ◽  
Integrated Analysis ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Progressive Neurodegeneration ◽  
Cns Effects

Enzyme replacement therapy (ERT) improves somatic manifestations in mucopolysaccharidoses (MPS). However, because intravenously administered enzymes cannot cross the blood–brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT in order to achieve CNS effects, but the burdens on patients are inimical to long-term administrations. However, since pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in a mouse model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT that is effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the previously obtained preclinical and clinical evidence related to the use of this drug, presents latest data, and discusses the preclinical, translational, and clinical challenges of evaluating, ameliorating, and preventing neurodegeneration in patients with MPS-II.

scholarly journals Current Approaches to the Treatment of Hunter Syndrome

2018 ◽  
Vol 15 (4) ◽  
pp. 324-332
Author(s):  
Ekaterina Yu. Zakharova ◽  
Elena Yu. Voskoboeva ◽  
Alla N. Semyachkina ◽  
Nato D. Vashakmadze ◽  
Amina I. Gamzatova ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Cell Transplantation ◽  
Hunter Syndrome ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked hereditary disorder associated with a deficiency of iduronate2-sulfatase (IDS). IDS deficiency provokes the accumulation of dermatan sulfate and heparan sulfate in different tissues. Clinical manifestations of MPS II are heterogeneous and involve different organs. Two phenotypes are distinguished: attenuated or severe; classification is based on central nervous system impairment signs. The review provides data on the current treatments opportunities for Hunter syndrome and perspectives for development of new therapeutic approaches. Current treatment includes intravenous enzyme replacement therapy (ERT), hematopoietic stem cell transplantation, and symptomatic treatment. Intravenous enzyme replacement therapy does not promote the enzyme to penetrate the blood-brain barrier which leads to the treatment failure for neurological signs and symptoms; hematopoietic stem cell transplantation has high risk of post-transplantation complications but can improve some neurological problems. Intrathecal ERT, substrate reduction, pharmacological chaperones, and gene therapy are currently under investigation as therapies for severe form of MPS II. Development of new approaches to treatment of Hunter syndrome and other hereditary diseases is extremely vital.

Clinical experience of replacing enzyme replacement therapy in a patient with mucopolysaccharidosis type II

2020 ◽  
Vol 1 (4) ◽  
pp. 242-247
Author(s):  
Lyudmila M. Kuzenkova ◽  
Tatyana V. Podkletnova ◽  
Lale A. Pak ◽  
Oksana A. Ereshko
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Hunter Syndrome ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Lysosomal Disease ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Child Patient

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an inherited chronic progressive lysosomal disease associated with recessive X-linked inheritance. MPS II is classified as an orphan disease and occurs at a rate of 1.3 per 100,000 white boys. Hunter syndrome is the most common type of mucopolysaccharidosis, accounting for about 50% of MPS types. The diseases pathogenesis is based on a violation of the stepwise cleavage of glycosaminoglycans (GAG) heparansulfate and dermatansulfate caused by a deficiency of the iduronate-2-sulfatase enzyme encoded by theIDSgene. The existing deficiency or complete absence of iduronate-2-sulfatase leads to a violation of the final stage of glycosaminoglycan catabolism and the accumulation heparansulfate and dermatansulfate in all organs and tissues. Currently, there are two drugs registered in the Russian Federation for pathogenetic enzyme replacement therapy of MPS: idursulfase and idursulfase beta. This refers to the expansion of the therapeutic options for Hunter syndrome patients in the event of severe adverse events. It allows choosing the treatment regimen that will be optimal for the patient and will significantly improve the quality of life. In this article, the authors share their own experience of changing enzyme replacement therapy in an MPS II child patient.

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