ArticleHuman gene therapy2014
Partial correction of the CNS lysosomal storage defect in a mouse model of juvenile neuronal ceroid lipofuscinosis by neonatal CNS administration of an adeno-associated virus serotype rh.10 vector expressing the human CLN3 gene.
Article in Human gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Reversible synaptic deficits in early-stage batten disease.Journal of translational medicine · 2026Article
- Nature Inspired Delivery Vehicles for CRISPR-Based Genome Editing.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Enteric nervous system degeneration in human and murine CLN3 disease, is ameliorated by gene therapy in mice.Acta neuropathologica communications · 2025Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- Gene therapy ameliorates neuromuscular pathology in CLN3 disease.Acta neuropathologica communications · 2025Article
- CLN3 disease disrupts very early postnatal hippocampal maturation.Scientific reports · 2025Article
- A mouse mutant deficient in both neuronal ceroid lipofuscinosis-associated proteins CLN3 and TPP1.Journal of inherited metabolic disease · 2023Article
- Early recognition of CLN3 disease facilitated by visual electrophysiology and multimodal imaging.Documenta ophthalmologica. Advances in ophthalmology · 2023Article
- [Application of adeno-associated virus-mediated gene therapy in lysosomal storage diseases].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Review
- Patient-Derived Induced Pluripotent Stem Cell Models for Phenotypic Screening in the Neuronal Ceroid Lipofuscinoses.Molecules (Basel, Switzerland) · 2021Review
- Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development.Biomolecules · 2021Review
- Review
- Therapeutic efficacy of antisense oligonucleotides in mouse models of CLN3 Batten disease.Nature medicine · 2020Article
- Review
- Therapeutic landscape for Batten disease: current treatments and future prospects.Nature reviews. Neurology · 2019Review
- Advances in the Treatment of Neuronal Ceroid Lipofuscinosis.Expert opinion on orphan drugs · 2019Article
- Longitudinal In Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency.Brain : a journal of neurology · 2018Article
- Prevention of Photoreceptor Cell Loss in a Cln6Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3).The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Juvenile neuronal ceroid lipofuscinosis (JNCL or CLN3 disease) is an autosomal recessive lysosomal storage disease resulting from mutations in the CLN3 gene that encodes a lysosomal membrane protein. The disease primarily affects the brain with widespread intralysosomal accumulation of autofluorescent material and fibrillary gliosis, as well as the loss of specific neuronal populations. As an experimental treatment for the CNS manifestations of JNCL, we have developed a serotype rh.10 adeno-associated virus vector expressing the human CLN3 cDNA (AAVrh.10hCLN3). We hypothesized that administration of AAVrh.10hCLN3 to the Cln3(Δex7/8) knock-in mouse model of JNCL would reverse the lysosomal storage defect, as well as have a therapeutic effect on gliosis and neuron loss. Newborn Cln3(Δex7/8) mice were administered 3 × 10(10) genome copies of AAVrh.10hCLN3 to the brain, with control groups including untreated Cln3(Δex7/8) mice and wild-type littermate mice. After 18 months, CLN3 transgene expression was detected in various locations throughout the brain, particularly in the hippocampus and deep anterior cortical regions. Changes in the CNS neuronal lysosomal accumulation of storage material were assessed by immunodetection of subunit C of ATP synthase, luxol fast blue staining, and periodic acid-Schiff staining. For all parameters, Cln3(Δex7/8) mice exhibited abnormal lysosomal accumulation, but AAVrh.10hCLN3 administration resulted in significant reductions in storage material burden. There was also a significant decrease in gliosis in AAVrh.10hCLN3-treated Cln3(Δex7/8) mice, and a trend toward improved neuron counts, compared with their untreated counterparts. These data demonstrate that AAVrh.10 delivery of a wild-type cDNA to the CNS is not harmful and instead provides a partial correction of the neurological lysosomal storage defect of a disease caused by a lysosomal membrane protein, indicating that this may be an effective therapeutic strategy for JNCL and other diseases in this category.
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