ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Intracranial delivery of CLN2 reduces brain pathology in a mouse model of classical late infantile neuronal ceroid lipofuscinosis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 171 citations in OpenAlex.
- Consequences of human genetic variations inMolecular therapy. Advances · 2026Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- Recreating pathophysiology of CLN2 disease and demonstrating reversion by TPP1 gene therapy in hiPSC-derived retinal organoids and retina-on-chip.Cell reports. Medicine · 2025Article
- Advances in AAV-mediated gene replacement therapy for pediatric monogenic neurological disorders.Molecular therapy. Methods & clinical development · 2024Review
- Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications.Advanced drug delivery reviews · 2024Review
- A mouse mutant deficient in both neuronal ceroid lipofuscinosis-associated proteins CLN3 and TPP1.Journal of inherited metabolic disease · 2023Article
- Sex specific molecular networks and key drivers of Alzheimer's disease.Molecular neurodegeneration · 2023Article
- Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2R207X mouse model.The Journal of clinical investigation · 2023Article
- A Novel Porcine Model of CLN2 Batten Disease that Recapitulates Patient Phenotypes.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses.Science advances · 2022Article
- A neglected neurodegenerative disease: Adult-onset globoid cell leukodystrophy.Frontiers in neuroscience · 2022Review
- Glial Dysfunction and Its Contribution to the Pathogenesis of the Neuronal Ceroid Lipofuscinoses.Frontiers in neurology · 2022Review
- Brain transcriptome analysis of a CLN2 mouse model as a function of disease progression.Journal of neuroinflammation · 2021Article
- Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development.Biomolecules · 2021Review
- Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord.Frontiers in molecular neuroscience · 2021Review
- Review
- Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum.Journal of biomedical science · 2020Review
- Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy.Therapeutics and clinical risk management · 2020Review
- Review
- Therapeutic landscape for Batten disease: current treatments and future prospects.Nature reviews. Neurology · 2019Review
10 more citing papers are in PubMed but not listed here.
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16 authors at 3 institutions in 1 country.
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Abstract
Classical late infantile neuronal ceroid lipofuscinosis (cLINCL) is a lysosomal storage disorder caused by mutations in CLN2, which encodes lysosomal tripeptidyl peptidase I (TPP1). Lack of TPP1 results in accumulation of autofluorescent storage material and curvilinear bodies in cells throughout the CNS, leading to progressive neurodegeneration and death typically in childhood. In this study, we injected adeno-associated virus (AAV) vectors containing the human CLN2 cDNA into the brains of CLN2(-/-) mice to determine therapeutic efficacy. AAV2CUhCLN2 or AAV5CUhCLN2 were stereotaxically injected into the motor cortex, thalamus, and cerebellum of both hemispheres at 6 weeks of age, and mice were then killed at 13 weeks after injection. Mice treated with AAV2CUhCLN2 and AAV5CUhCLN2 contained TPP1 activity at each injection tract that was equivalent to 0.5- and 2-fold that of CLN2(+/+) control mice, respectively. Lysosome-associated membrane protein 1 immunostaining and confocal microscopy showed intracellular targeting of TPP1 to the lysosomal compartment. Compared with control animals, there was a marked reduction of autofluorescent storage in the AAV2CUhCLN2 and AAV5CUhCLN2 injected brain regions, as well as adjacent regions, including the striatum and hippocampus. Analysis by electron microscopy confirmed a significant decrease in pathological curvilinear bodies in cells. This study demonstrates that AAV-mediated TPP1 enzyme replacement corrects the hallmark cellular pathologies of cLINCL in the mouse model and raises the possibility of using AAV gene therapy to treat cLINCL patients.
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