Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice

Baldo, Guilherme; Mayer, Fabiana Quoos; Martinelli, Barbara; Carvalho, Talita Giacomet de; Meyer, Fabíola Schons; Oliveira, Patrícia Gnieslaw de; Meurer, Luíse; Tavares, Ângela Maria Vicente; Matte, Úrsula; Giugliani, Roberto

doi:10.1016/j.ymgme.2013.03.005

Cited by 58 publications

(57 citation statements)

References 28 publications

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“…ERT started at birth for MPS I mice did not show any marked benefits for bone and joint development [58]. These observations suggest that conventional ERT alone, even when started at birth, cannot completely prevent bone pathology in MPS mice.…”

Section: Enzyme Replacement Therapy (Ert)mentioning

confidence: 78%

“…Newborn ERT for MPS I mice improves visceral organ and brain development [58]; but bone and joints showed only partial or no benefit. The avascular bone and joint were difficult to correct, despite early treatment.…”

Section: Enzyme Replacement Therapy (Ert)mentioning

confidence: 94%

“…Newborn or early ERTs prove a better resolution in bone morphology and clearance of storage materials [60][61] although vacuolated materials are still observed in chondrocytes. Discrepancy of therapeutic effect of newborn ERT among species may be related to kinetics and biodistribution of the enzyme [58].…”

Section: Enzyme Replacement Therapy (Ert)mentioning

confidence: 99%

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Therapies for the bone in mucopolysaccharidoses

Tomatsu

Barrera

Alméciga-Díaz

et al. 2015

Molecular Genetics and Metabolism

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Patients with mucopolysaccharidoses (MPS) have accumulation of glycosaminoglycans in multiple tissues which may cause coarse facial features, mental retardation, recurrent ear and nose infections, inguinal and umbilical hernias, hepatosplenomegaly, and skeletal deformities. Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. Patients with MPS are often wheelchair-bound and physical handicaps increase with age as a result of progressive skeletal dysplasia, abnormal joint mobility, and osteoarthritis, leading to 1) stenosis of the upper cervical region, 2) restrictive small lung, 3) hip dysplasia, 4) restriction of joint movement, and 5) surgical complications. Patients often need multiple orthopedic procedures including cervical decompression and fusion, carpal tunnel release, hip reconstruction and replacement, and femoral or tibial osteotomy through their lifetime. Current measures to intervene in bone disease progression are not perfect and palliative, and improved therapies are urgently required.Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy are available or in development for some types of MPS. Delivery of sufficient enzyme to bone, especially avascular cartilage, to prevent or ameliorate the devastating skeletal dysplasias remains an unmet challenge. The use of an anti-inflammatory drug is also under clinical study. Therapies should start at a very early stage prior to irreversible bone lesion, and damage since the severity of skeletal dysplasia is associated with level of activity during daily life.This review illustrates a current overview of therapies and their impact for bone lesions in MPS including ERT, HSCT, gene therapy, and anti-inflammatory drugs.

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Section: Enzyme Replacement Therapy (Ert)mentioning

confidence: 78%

Section: Enzyme Replacement Therapy (Ert)mentioning

confidence: 94%

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Therapies for the bone in mucopolysaccharidoses

Tomatsu

Barrera

Alméciga-Díaz

et al. 2015

Molecular Genetics and Metabolism

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“…Several MPS-subtypes have specific enzyme replacement therapy available, and there are many indications that MPS patients treated at an early age do better than those treated later in life (Auclair et al, 2003;McGill et al, 2010;Gabrielli et al, 2010;Schulze-Frenking et al, 2011;Baldo et al, 2013;Poe et al, 2014;Muenzer J, 2014;Tomatsu et al, 2016). Newborn screening programs for MPSs using dried blood spots (DBS) were proposed in 2001 and highthroughput technologies such as tandem mass spectrometry (MS/MS) are now under investigation (Meikle et al, 2006;Gelb et al, 2006;Wolfe et al, 2011;de Ruijter et al, 2012;Spacil et al, 2013;Scott et al, 2013;Lin et al, 2013;Tomatsu et al, 2013;Shimada et al, 2014a;Liao et al, 2014;Gucciardi et al, 2014;Ruijter et al, 2014;Gelb et al, 2015;Hopkins et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

Kubaski

Mason

Nakatomi

et al. 2017

Molecular Genetics and Metabolism

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“…Firstly, the inability of the relatively large enzyme to traffic through the poorly vascularized matrix of growth plates and other cartilaginous tissue to target cells (Aldenhoven et al 2009;Baldo et al 2013). Secondly, cartilage cells are derived from mesenchymal stem cells, which are not transplanted in sufficient amounts by HSCT (Koç et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model

et al. 2015

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Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by diminished degradation of the glycosaminoglycans heparan sulfate (HS) and dermatan sulfate (DS). Patients present with a variety of symptoms, including severe skeletal disease. Current therapeutic strategies have only limited effects on bone disease. The isoflavone genistein has been studied as a potential therapy for the mucopolysaccharidoses because of its putative ability to inhibit GAG synthesis and subsequent accumulation. Cell, animal, and clinical studies, however, showed variable outcomes. To determine the effects of genistein on MPS I-related bone disease, wild-type (WT) and MPS I mice were fed a genistein-supplemented diet (corresponding to a dose of approximately 160 mg/kg/day) for 8 weeks. HS and DS levels in bone and plasma remained unchanged after genistein supplementation, while liver HS levels were decreased in genistein-fed MPS I mice as compared to untreated MPS I mice. Unexpectedly, genistein-fed mice exhibited significantly decreased body length and femur length. In addition, 60% of genistein-fed MPS I mice developed a scrotal hernia and/or scrotal hydrocele, manifestations ,which were absent in WT or untreated MPS I mice. In contrast to studies in MPS III mice, our study in MPS I mice demonstraes no beneficial but even potential adverse effects of genistein supplementation. Our results urge for a cautious approach on the use of genistein, at least in patients with MPS I.

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Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice

Cited by 58 publications

References 28 publications

Therapies for the bone in mucopolysaccharidoses

Therapies for the bone in mucopolysaccharidoses

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model

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