Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network

Salazar, Diego; Rodríguez-López, Alexander; Herreño, Angélica María; Barbosa, Hector; Herrera, Juliana; Ardila, Andrea; Barreto, George E.; González, Janneth; Alméciga-Díaz, Carlos J.

doi:10.1016/j.ymgme.2015.08.001

Cited by 25 publications

(21 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using these data, pathway analysis succeeded in identifying the main disrupted pathways. Salazar et al [31] reported a genome-scale human metabolic reconstruction based approach to understand the effect of metabolism alterations in MPS. This in silico approach applied to MPS III subtypes (MPS IIIA, MPS IIIB, MPS IIIC and MPS IIID) by silencing, respectively, SGSH, NAGLU, HGSNAT and GNS genes, allowed the generation of models which were analyzed through flux balance and variability analysis.…”

Section: Discussionmentioning

confidence: 99%

Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis

et al. 2018

View full text Add to dashboard Cite

BackgroundMetabolomics represent a valuable tool to recover biological information using body fluids and may help to characterize pathophysiological mechanisms of the studied disease. This approach has not been widely used to explore inherited metabolic diseases. This study investigates mucopolysaccharidosis type III (MPS III). A thorough and holistic understanding of metabolic remodeling in MPS III may allow the development, improvement and personalization of patient care.MethodsWe applied both targeted and untargeted metabolomics to urine samples obtained from a French cohort of 49 patients, consisting of 13 MPS IIIA, 16 MPS IIIB, 13 MPS IIIC, and 7 MPS IIID, along with 66 controls. The analytical strategy is based on ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry. Twenty-four amino acids have been assessed using tandem mass spectrometry combined with liquid chromatography. Multivariate data modeling has been used for discriminant metabolite selection. Pathway analysis has been performed to retrieve metabolic pathways impairments.ResultsData analysis revealed distinct biochemical profiles. These metabolic patterns, particularly those related to the amino acid metabolisms, allowed the different studied groups to be distinguished. Pathway analysis unveiled major amino acid pathways impairments in MPS III mainly arginine–proline metabolism and urea cycle metabolism.ConclusionThis represents one of the first metabolomics-based investigations of MPS III. These results may shed light on MPS III pathophysiology and could help to set more targeted studies to infer the biomarkers of the affected pathways, which is crucial for rare conditions such as MPS III.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1625-1) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Recently, a new set of AAV vectors carrying both GALNS and SUMF1 genes were evaluated using internal ribosome entry site (IRES), which allowed higher enzyme activity than that observed with GALNS and SUMF1 genes be transduced with separated vectors [155]. Finally, GALNS transduction mediated by the lentiviral vectors in HEK293 cells and Morquio A skin fibroblasts showed enzyme activity levels 100-fold higher than those observed by using AAV vectors, as well as the normalization of β-hexosaminidase and β-galactosidase activity [155], which has been reported as secondary biomarkers for Morquio A [28,156]. …”

Section: Therapy and Managementmentioning

confidence: 99%

Mucopolysaccharidosis IVA and glycosaminoglycans

Khan

Alméciga-Díaz

Sawamoto

et al. 2017

Molecular Genetics and Metabolism

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Martell A systems biology approach using genome-scale human metabolic reconstruction has been studied by Salazar and colleagues in an effort to discover additional biomarkers for MPS [43].…”

Section: Assessment Of Potential Biomarkersmentioning

confidence: 99%

Elosulfase alfa (BMN 110) for the treatment of mucopolysaccharidosis IVA (Morquio A Syndrome)

Hendriksz

2016

Expert Review of Clinical Pharmacology

View full text Add to dashboard Cite

Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network

Cited by 25 publications

References 71 publications

Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis

Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis

Mucopolysaccharidosis IVA and glycosaminoglycans

Elosulfase alfa (BMN 110) for the treatment of mucopolysaccharidosis IVA (Morquio A Syndrome)

Contact Info

Product

Resources

About