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 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.

Two siblings with attenuated MPS II form: Long term enzyme replacement therapy

2021 ◽  
Vol 132 (2) ◽  
pp. S107-S108
Author(s):  
Nato Vashakmadze ◽  
Leyla Namazova-Baranova ◽  
Natalia Zhurkova ◽  
Olga Gordeeva ◽  
Nina Fedorova ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Enzyme Replacement ◽  
Mps Ii

Long-term biomarker and cognitive follow-up of children with Hunter syndrome receiving intrathecal enzyme replacement therapy

2015 ◽  
Vol 114 (2) ◽  
pp. S83 ◽  
Author(s):  
Joseph Muenzer ◽  
Christian J. Hendriksz ◽  
Margot B. Stein ◽  
Zheng Fan ◽  
Shauna Kearney ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Hunter Syndrome ◽  
Enzyme Replacement

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 Long-term experience with enzyme replacement therapy (ERT) in MPS II patients with a severe phenotype: an international case series

2014 ◽  
Vol 37 (5) ◽  
pp. 823-829 ◽  
Author(s):  
Christina Lampe ◽  
Ann-Kathrin Bosserhoff ◽  
Barbara K. Burton ◽  
Roberto Giugliani ◽  
Carolina F. de Souza ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Case Series ◽  
Severe Phenotype ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Long Term Experience

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.

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