Gene therapy of metachromatic leukodystrophy
- 1 January 2005
- journal article
- review article
- Published by Taylor & Francis in Expert Opinion on Biological Therapy
- Vol. 5 (1) , 55-65
- https://doi.org/10.1517/14712598.5.1.55
Abstract
Metachromatic leukodystrophy (MLD) is a lysosomal storage disease that is caused by a deficiency of arylsulfatase A (ASA). The deficiency results in the intralysosomal accumulation of the acidic sphingolipid 3-O-sulfogalactosyl-ceramide (sulfatide). Patients suffer from progressive demyelination and die from multiple neurological deficits. Curative treatment is not available. ASA bears mannose 6-phosphate residues which function as recognition markers in endosome/lysosome-specific targeting pathways. The endocytic targeting route can be exploited to deliver exogeneous ASA to the lysosomes of ASA-deficient cells. ASA knockout mice, which develop a disorder related to MLD, have therefore been treated by exvivo and invivo gene therapy. Following transplantation of bone marrow cells overexpressing ASA from a retroviral vector, donor-type cells secrete ASA, which is endocytosed by recipient cells. The enzyme transfer results in the metabolic cross-correction of recipient cells and the improvement of biochemica...Keywords
This publication has 39 references indexed in Scilit:
- Metachromatic leukodystrophy: consequences of sulphatide accumulationActa Paediatrica, 2003
- Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophagesBiochemical Journal, 2002
- α-L-Iduronidase and enzyme replacement therapy for mucopolysaccharidosis IExpert Opinion on Biological Therapy, 2002
- Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestationsGene Therapy, 2002
- Long-term expression and transfer of arylsulfatase A into brain of arylsulfatase A-deficient mice transplanted with bone marrow expressing the arylsulfatase A cDNA from a retroviral vectorGene Therapy, 2000
- Retrovirally expressed human arylsulfatase A corrects the metabolic defect of arylsulfatase A-deficient mouse cellsGene Therapy, 2000
- Transduction of fibroblasts and CD34+ progenitors using a selectable retroviral vector containing cDNAs encoding arylsulfatase A and CD24Journal of Human Genetics, 2000
- Transduced Fibroblasts and Metachromatic Leukodystrophy Lymphocytes Transfer Arylsulfatase A to Myelinating Glia and Deficient CellsIn VitroHuman Gene Therapy, 1998
- Overexpression of human alpha-galactosidase A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion.The Journal of cell biology, 1992
- Inborn Errors of Mucopolysaccharide MetabolismScience, 1970