ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Enzyme replacement improves ataxic gait and central nervous system histopathology in a mouse model of metachromatic leukodystrophy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 66 citations in OpenAlex.
- Intravenous arylsulfatase A in metachromatic leukodystrophy: a phase 1/2 study.Annals of clinical and translational neurology · 2021Trial
- Dose-response evaluation of intravenous gene therapy in a symptomatic mouse model of metachromatic leukodystrophy.Molecular therapy. Methods & clinical development · 2024Article
- Engineered arylsulfatase A with increased activity, stability and brain delivery for therapy of metachromatic leukodystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice.Frontiers in molecular neuroscience · 2021Article
- Intravenous delivery for treatment of mucopolysaccharidosis type I: A comparison of AAV serotypes 9 and rh10.Molecular genetics and metabolism reports · 2020Article
- A Highly Efficacious PS Gene Editing System Corrects Metabolic and Neurological Complications of Mucopolysaccharidosis Type I.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Alpha-Mannosidosis: Therapeutic Strategies.International journal of molecular sciences · 2018Review
- Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by ZFN-Mediated In Vivo Genome Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Nonclinical comparability studies of recombinant human arylsulfatase A addressing manufacturing process changes.PloS one · 2018Article
- Gene therapy for lysosomal storage disorders: recent advances for metachromatic leukodystrophy and mucopolysaccaridosis I.Journal of inherited metabolic disease · 2017Review
- Chronic enzyme replacement therapy ameliorates neuropathology in alpha-mannosidosis mice.Annals of clinical and translational neurology · 2015Article
- Effect of systemic high dose enzyme replacement therapy on the improvement of CNS defects in a mouse model of mucopolysaccharidosis type II.Orphanet journal of rare diseases · 2015Article
- Arylsulfatase A Overexpressing Human iPSC-derived Neural Cells Reduce CNS Sulfatide Storage in a Mouse Model of Metachromatic Leukodystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Lysosomal storage disease: gene therapy on both sides of the blood-brain barrier.Molecular genetics and metabolism · 2015Review
- Gene therapy for the neurological manifestations in lysosomal storage disorders.Journal of lipid research · 2014Review
- Long-term correction of biochemical and neurological abnormalities in MLD mice model by neonatal systemic injection of an AAV serotype 9 vector.Gene therapy · 2014Article
- Comparison of five peptide vectors for improved brain delivery of the lysosomal enzyme arylsulfatase A.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- High-dose enzyme replacement therapy in murine Hurler syndrome.Molecular genetics and metabolism · 2014Article
- Direct tandem mass spectrometric profiling of sulfatides in dry urinary samples for screening of metachromatic leukodystrophy.Clinica chimica acta; international journal of clinical chemistry · 2013Article
- Blood-brain barrier structure and function and the challenges for CNS drug delivery.Journal of inherited metabolic disease · 2013Review
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inherited deficiencies of lysosomal hydrolases cause lysosomal storage diseases (LSDs) that are characterized by a progressive multisystemic pathology and premature death. Repeated intravenous injection of the active counterpart of the deficient enzyme, a treatment strategy called enzyme replacement therapy (ERT), evolved as a clinical option for several LSDs without central nervous system (CNS) involvement. To assess the efficacy of long-term ERT in metachromatic leukodystrophy (MLD), an LSD with prevailing nervous system disease, we treated immunotolerant arylsulfatase A (ASA) knockout mice with 52 doses of either 4 or 50 mg/kg recombinant human ASA (rhASA). ERT was tolerated without side effects and improved disease manifestations in a dose-dependent manner. Dosing of 4 mg/kg diminished sulfatide storage in kidney and peripheral nervous system (PNS) but not the CNS, whereas treatment with 50 mg/kg was also effective in the CNS in reducing storage in brain and spinal cord by 34 and 45%, respectively. Histological analyses revealed regional differences in sulfatide clearance. While 70% less storage profiles were detectable, for example, in the hippocampal fimbria, the histopathology of the brain stem was unchanged. Both enzyme doses normalized the ataxic gait of ASA knockout mice, demonstrating prevention of nervous system dysfunctions that dominate early stages of MLD.
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