Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses
Mucopolysaccharidoses (MPSs) are inherited metabolic diseases caused by the deficiency of lysosomal enzymes needed to catabolize glycosaminoglycans (GAGs). Four therapeutic options are currently considered: enzyme replacement therapy, substrate reduction therapy, gene therapy, and hematopoietic stem...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-09-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050118300482 |
| _version_ | 1819112912361357312 |
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| author | Valeria De Pasquale Patrizia Sarogni Valeria Pistorio Giuliana Cerulo Simona Paladino Luigi Michele Pavone |
| author_facet | Valeria De Pasquale Patrizia Sarogni Valeria Pistorio Giuliana Cerulo Simona Paladino Luigi Michele Pavone |
| author_sort | Valeria De Pasquale |
| collection | DOAJ |
| description | Mucopolysaccharidoses (MPSs) are inherited metabolic diseases caused by the deficiency of lysosomal enzymes needed to catabolize glycosaminoglycans (GAGs). Four therapeutic options are currently considered: enzyme replacement therapy, substrate reduction therapy, gene therapy, and hematopoietic stem cell transplantation. However, while some of them exhibit limited clinical efficacy and require high costs, others are still in development. Therefore, alternative treatments for MPSs need to be explored. Here we describe an innovative therapeutic approach based on the use of a recombinant protein that is able to bind the excess of extracellular accumulated heparan sulfate (HS). We demonstrate that this protein is able to reduce lysosomal defects in primary fibroblasts from MPS I and MPS IIIB patients. We also show that, by masking the excess of extracellular accumulated HS in MPS fibroblasts, fibroblast growth factor (FGF) signal transduction can be positively modulated. We, therefore, suggest the use of a competitive binding molecule for HS in MPSs as an alternative strategy to prevent the detrimental extracellular substrate storage. Keywords: cell signaling, fibroblast growth factor, glycosaminoglycan, heparan sulfate, lysosomal storage diseases, mucopolysaccharidosis |
| first_indexed | 2024-12-22T04:21:03Z |
| format | Article |
| id | doaj.art-0a95da95c6a04cbc8f1dec282116e797 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-22T04:21:03Z |
| publishDate | 2018-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-0a95da95c6a04cbc8f1dec282116e7972022-12-21T18:39:17ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012018-09-0110816Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for MucopolysaccharidosesValeria De Pasquale0Patrizia Sarogni1Valeria Pistorio2Giuliana Cerulo3Simona Paladino4Luigi Michele Pavone5Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, Italy; Corresponding author: Luigi Michele Pavone, Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.Mucopolysaccharidoses (MPSs) are inherited metabolic diseases caused by the deficiency of lysosomal enzymes needed to catabolize glycosaminoglycans (GAGs). Four therapeutic options are currently considered: enzyme replacement therapy, substrate reduction therapy, gene therapy, and hematopoietic stem cell transplantation. However, while some of them exhibit limited clinical efficacy and require high costs, others are still in development. Therefore, alternative treatments for MPSs need to be explored. Here we describe an innovative therapeutic approach based on the use of a recombinant protein that is able to bind the excess of extracellular accumulated heparan sulfate (HS). We demonstrate that this protein is able to reduce lysosomal defects in primary fibroblasts from MPS I and MPS IIIB patients. We also show that, by masking the excess of extracellular accumulated HS in MPS fibroblasts, fibroblast growth factor (FGF) signal transduction can be positively modulated. We, therefore, suggest the use of a competitive binding molecule for HS in MPSs as an alternative strategy to prevent the detrimental extracellular substrate storage. Keywords: cell signaling, fibroblast growth factor, glycosaminoglycan, heparan sulfate, lysosomal storage diseases, mucopolysaccharidosishttp://www.sciencedirect.com/science/article/pii/S2329050118300482 |
| spellingShingle | Valeria De Pasquale Patrizia Sarogni Valeria Pistorio Giuliana Cerulo Simona Paladino Luigi Michele Pavone Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses Molecular Therapy: Methods & Clinical Development |
| title | Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses |
| title_full | Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses |
| title_fullStr | Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses |
| title_full_unstemmed | Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses |
| title_short | Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses |
| title_sort | targeting heparan sulfate proteoglycans as a novel therapeutic strategy for mucopolysaccharidoses |
| url | http://www.sciencedirect.com/science/article/pii/S2329050118300482 |
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