Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I

Pievani, Alice; Azario, Isabella; Antolini, Laura; Shimada, Tsutomu; Patel, Pravin; Remoli, Cristina; Rambaldi, Benedetta; Valsecchi, Maria Grazia; Riminucci, Mara; Biondi, Andrea; Tomatsu, Shunji; Serafini, Marta

doi:10.1182/blood-2014-06-581207

Cited by 39 publications

(39 citation statements)

References 39 publications

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“…Initiating these treatments at birth or a very early stage provides the greatest therapeutic effect on the clinical course of the disease (1-8). To improve activities of daily living (ADL) for patients, early diagnosis and early treatment are critical.…”

Section: Introductionmentioning

confidence: 99%

“…We developed a method that can assay CS, DS, HS, and KS simultaneously in blood and/or urine samples using high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) for MPS (10-21). The LC-MS/MS method not only shows sensitivity and specificity for detecting all subtypes of MPS but is also able to monitor therapeutic efficacy in MPS patients and animal models (1, 8, 13, 14, 17-20, 23-25). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Newborn screening for mucopolysaccharidoses by GAG assay with tandem mass spectrometry

Tomatsu

Kubaski

Mason

et al. 2018

Molecular Genetics and Metabolism

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Newborn screening for mucopolysaccharidoses by GAG assay with tandem mass spectrometry

Tomatsu

Kubaski

Mason

et al. 2018

Molecular Genetics and Metabolism

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“…We have tested the hypothesis that HSCT at birth can prevent skeletal dysplasia in MPS I mice [105]. Newborn BMT was effective at restoring α-iduronidase (IDUA) activity and preventing elevated glycosaminoglycans in blood and multiple organs.…”

Section: Hsct At Birth-a Few Studies Have Evaluated the Effect Of Hscmentioning

confidence: 99%

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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“…Skeletal disease manifestations, and to some extent spinal disease in MPS I, II, IIIA, IVA, VII, and IX, have all been studied in murine models [68–75]. Murine models have also proven particularly useful for assaying the efficacy of gene therapy and enzyme replacement therapy in alleviating disease symptoms [76–82] as they are biochemically and developmentally well-understood, relatively easy to produce, and can be bred in large, genetically homogenous quantities. Measurements of vertebral bone formation in murine MPS models through bone volume and bone mass measurements as well as bone length and growth plate heights in have shown decreased bone growth, lower hypertrophy in growth plate chondrocytes, and abnormal skeletal development [27, 68, 69, 73–75, 83, 84].…”

Section: Pathophysiology Of Spine Disease In Mpsmentioning

confidence: 99%

Pathogenesis and treatment of spine disease in the mucopolysaccharidoses

Peck

Casal

Malhotra

et al. 2016

Molecular Genetics and Metabolism

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The mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans (GAGs). Skeletal disease is common in MPS patients, with the severity varying both within and between subtypes. Within the spectrum of skeletal disease, spinal manifestations are particularly prevalent. Developmental and degenerative abnormalities affecting the substructures of the spine can result in compression of the spinal cord and associated neural elements. Resulting neurological complications, including pain and paralysis, significantly reduce patient quality of life and life expectancy. Systemic therapies for MPS such as hematopoietic stem cell transplantation and enzyme replacement therapy have shown limited efficacy for improving spinal manifestations in patients and animal models, and there is therefore a pressing need for new therapeutic approaches that specifically target this debilitating aspect of the disease. In this review, we examine how pathological abnormalities affecting the key substructures of the spine – the discs, vertebrae, odontoid process and dura – contribute to the progression of spinal deformity and symptomatic compression of neural elements. Specifically, we review current understanding of the underlying pathophysiology of spine disease in MPS, how the tissues of the spine respond to current clinical and experimental treatments, and discuss future strategies for improving the efficacy of these treatments.

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Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I

Abstract: Key Points Allogeneic BMT into newborn MPS I mice allows high donor-derived hematopoietic engraftment and prevents bone deformities. Bones of transplanted MPS I mice show significant improvements at radiographic, microcomputed tomography, and histological analyses.

Cited by 39 publications

References 39 publications

Newborn screening for mucopolysaccharidoses by GAG assay with tandem mass spectrometry

Newborn screening for mucopolysaccharidoses by GAG assay with tandem mass spectrometry

Therapies for the bone in mucopolysaccharidoses

Pathogenesis and treatment of spine disease in the mucopolysaccharidoses

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