Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: Early treatment rescues bone lesions?

Tomatsu, Shunji; Montaño, Adriana M.; Oikawa, Hirotaka; Dũng, Vũ Chí; Hashimoto, Amiko; Oguma, Toshihiro; Gutiérrez, Mónica A.; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S.

doi:10.1016/j.ymgme.2014.05.013

Cited by 29 publications

(15 citation statements)

References 50 publications

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“…All together, these cases underline the importance of early treatment. Animal studies on MPS mice are consistent with these findings [144,182,183]. According to these data on newborn MPS mice and human MPS siblings, there is no doubt that newborn screening is needed for all the MPS that can benefit from an etiologic treatment.…”

Section: Ert In Siblingssupporting

confidence: 60%

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

Parini

Deodato

2020

IJMS

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The aim of this review is to summarize the evidence on efficacy, effectiveness and safety of intravenous enzyme replacement therapy (ERT) available for mucopolysaccharidoses (MPSs) I, II, IVA, VI and VII, gained in phase III clinical trials and in observational post-approval studies. Post-marketing data are sometimes conflicting or controversial, possibly depending on disease severity, differently involved organs, age at starting treatment, and development of anti-drug antibodies (ADAs). There is general agreement that ERT is effective in reducing urinary glycosaminoglycans and liver and spleen volume, while heart and joints outcomes are variable in different studies. Effectiveness on cardiac valves, trachea and bronchi, hearing and eyes is definitely poor, probably due to limited penetration in the specific tissues. ERT does not cross the blood–brain barrier, with the consequence that the central nervous system is not cured by intravenously injected ERT. All patients develop ADAs but their role in ERT tolerance and effectiveness has not been well defined yet. Lack of reliable biomarkers contributes to the uncertainties about effectiveness. The data obtained from affected siblings strongly indicates the need of neonatal screening for treatable MPSs. Currently, other treatments are under evaluation and will surely help improve the prognosis of MPS patients.

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Section: Ert In Siblingssupporting

confidence: 60%

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

Parini

Deodato

2020

IJMS

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“…In the growth plate, ligaments, articular cartilage, and articular disc, the storage materials (vacuoles) were reduced but still remained to a variable extent although cellular organization was improved [118]. …”

Section: Therapy and Managementmentioning

confidence: 99%

Mucopolysaccharidosis IVA and glycosaminoglycans

Khan

Alméciga-Díaz

Sawamoto

et al. 2017

Molecular Genetics and Metabolism

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Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA.

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“…Enzyme replacement therapy (ERT) [3][4][5], hematopoietic stem cell transplantation (HSCT) [6][7][8][9], substrate reduction therapy (SRT) [10,11], gene therapy [12,13], and anti-inflammatory drugs [14,15] are in clinical use or being investigated under clinical trials for patients with some types of MPS. Initiating these treatments at birth or during early stages provides most benefits in the clinical improvement of the disease.…”

Section: Introductionmentioning

confidence: 99%

Establishment of glycosaminoglycan assays for mucopolysaccharidoses

Tomatsu

Shimada

Mason

et al. 2015

Molecular Genetics and Metabolism

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Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A range of methods have been developed to measure specific GAGs in various human samples to investigate diagnosis, prognosis, pathogenesis, GAG interaction with other molecules, and monitoring therapeutic efficacy. We OPEN ACCESSMetabolites 2014, 4 656 established ELISA, liquid chromatography tandem mass spectrometry (LC-MS/MS), and an automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes (ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have a high sensitivity and specificity in GAG analysis, applicable to the analysis of blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible with the standard equipment. HT-MS/MS yields higher throughput than conventional LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic step and cannot distinguish GAGs with identical molecular weights, leading to a limitation of measurements for some specific GAGs. Here we review the advantages and disadvantages of these methods for measuring GAG levels in biological specimens. We also describe an unexpected secondary elevation of keratan sulfate in patients with MPS that is an indirect consequence of disruption of catabolism of other GAGs.

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Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: Early treatment rescues bone lesions?

Cited by 29 publications

References 50 publications

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

Mucopolysaccharidosis IVA and glycosaminoglycans

Establishment of glycosaminoglycan assays for mucopolysaccharidoses

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