ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Distribution of a lysosomal enzyme in the adult brain by axonal transport and by cells of the rostral migratory stream.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 132 citations in OpenAlex.
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- Evolving therapies in neuronopathic LSDs: opportunities and challenges.Metabolic brain disease · 2022Review
- AAV gene therapy for Tay-Sachs disease.Nature medicine · 2022Article
- Routes of administration for adeno-associated viruses carrying gene therapies for brain diseases.Frontiers in molecular neuroscience · 2022Review
- Therapeutic benefit after intracranial gene therapy delivered during the symptomatic stage in a feline model of Sandhoff disease.Gene therapy · 2021Article
- Clinical Trials for Gene Therapy in Lysosomal Diseases With CNS Involvement.Frontiers in molecular biosciences · 2021Review
- Global CNS correction in a large brain model of human alpha-mannosidosis by intravascular gene therapy.Brain : a journal of neurology · 2020Article
- AAVrh10 Vector Corrects Disease Pathology in MPS IIIA Mice and Achieves Widespread Distribution of SGSH in Large Animal Brains.Molecular therapy. Methods & clinical development · 2020Article
- A novel gene editing system to treat both Tay-Sachs and Sandhoff diseases.Gene therapy · 2020Article
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- In Situ Hybridization for Detection of AAV-Mediated Gene Expression.Methods in molecular biology (Clifton, N.J.) · 2019Article
- In Vivo Selection of a Computationally Designed SCHEMA AAV Library Yields a Novel Variant for Infection of Adult Neural Stem Cells in the SVZ.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Adeno-associated viral gene therapy for mucopolysaccharidoses exhibiting neurodegeneration.Journal of molecular medicine (Berlin, Germany) · 2017Review
- Direct Intracranial Injection of AAVrh8 Encoding Monkey β-N-Acetylhexosaminidase Causes Neurotoxicity in the Primate Brain.Human gene therapy · 2017Article
- Article
- Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan.Human molecular genetics · 2015Article
- Ex vivo gene therapy using patient iPSC-derived NSCs reverses pathology in the brain of a homologous mouse model.Stem cell reports · 2015Article
- Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease.Gene therapy · 2015Article
- Bilateral single-site intracerebral injection of a nonpathogenic herpes simplex virus-1 vector decreases anxiogenic behavior in MPS VII mice.Molecular therapy. Methods & clinical development · 2015Article
- Gene therapy for the nervous system: challenges and new strategies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2014Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
A portion of the lysosomal enzymes produced by cells is secreted, diffuses through extracellular spaces, and can be taken up by distal cells via mannose-6-phosphate receptor-mediated endocytosis. This provides the basis for treating lysosomal storage diseases, many of which affect the CNS. Normal enzyme secreted from a cluster of genetically corrected cells has been shown to reverse storage lesions in a zone of surrounding brain tissue in mouse disease models. However, low levels of enzyme activity and reduction of storage lesions also have been observed at sites in the brain that may not be explained by a contiguous gradient of secreted enzyme diffusing away from the genetically corrected cells. No direct evidence for alternative mechanisms of enzyme transport has been shown, and little is understood about the intracellular movement of lysosomal enzymes in neurons. We investigated whether axonal transport could occur, by expressing an eukaryotic lysosomal enzyme that can be visualized in tissue sections (beta-glucuronidase) in brain structures that have defined axonal connections to other structures. This resulted in the transfer of enzyme to, and a reversal of storage lesions in, neurons that project to the gene expression site, but not in nearby structures that would have been corrected if the effect had been mediated by diffusion. In addition, transduction of cells in the subventricular zone resulted in the uptake of beta-glucuronidase by cells entering the rostral migratory stream. Gene transfer to specific neuronal circuits or cells in migratory pathways may facilitate delivery to the global brain lesions found in these disorders.
Indexed as
Identifiers
12151523PMC6758166W1601499949What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.