ArticleExperimental neurology2008
Survival advantage of neonatal CNS gene transfer for late infantile neuronal ceroid lipofuscinosis.
Article in Experimental neurology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Slowing late infantile Batten disease by direct brain parenchymal administration of a rh.10 adeno-associated virus expressingScience translational medicine · 2020Trial
- Clinical response to systemic AAV gene therapy in a large animal model of late-stage lysosomal storage disease.Gene therapy · 2026Article
- PPARα and RXRα in the regulation of neuronal ceroid lipofuscinosis genes: implications for Batten disease therapy.NeuroImmune pharmacology and therapeutics · 2026Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- Effect of disease progression on CSF-directed AAV gene therapy in a large brain animal model of lysosomal storage disease.Molecular therapy. Methods & clinical development · 2025Article
- Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease.Human gene therapy · 2023Article
- Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2R207X mouse model.The Journal of clinical investigation · 2023Article
- Catching Them Early: Framework Parameters and Progress for Prenatal and Childhood Application of Advanced Therapies.Pharmaceutics · 2022Review
- CRISPR Gene-Editing Models Geared Toward Therapy for Hereditary and Developmental Neurological Disorders.Frontiers in pediatrics · 2021Review
- Review
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Upregulation of tripeptidyl-peptidase 1 by 3-hydroxy-(2,2)-dimethyl butyrate, a brain endogenous ligand of PPARα: Implications for late-infantile Batten disease therapy.Neurobiology of disease · 2019Article
- Advances in the Treatment of Neuronal Ceroid Lipofuscinosis.Expert opinion on orphan drugs · 2019Article
- AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease.Human gene therapy. Clinical development · 2018Article
- Inducible transgenic expression of tripeptidyl peptidase 1 in a mouse model of late-infantile neuronal ceroid lipofuscinosis.PloS one · 2018Article
- Safety and potential efficacy of gemfibrozil as a supportive treatment for children with late infantile neuronal ceroid lipofuscinosis and other lipid storage disorders.Orphanet journal of rare diseases · 2017Review
- Chronic Enzyme Replacement to the Brain of a Late Infantile Neuronal Ceroid Lipofuscinosis Mouse Has Differential Effects on Phenotypes of Disease.Molecular therapy. Methods & clinical development · 2017Article
- Gene therapy for metachromatic leukodystrophy.Journal of neuroscience research · 2016Review
- Timing of Gene Therapy Interventions: The Earlier, the Better.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis.Orphanet journal of rare diseases · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal autosomal recessive neurodegenerative lysosomal storage disorder of childhood, is caused by mutations in the CLN2 gene, resulting in deficiency of the protein tripeptidyl peptidase I (TPP-I). We have previously shown that direct CNS administration of AAVrh.10hCLN2 to adult CLN2 knockout mice, a serotype rh.10 adeno-associated virus expressing the wild-type CLN2 cDNA, will partially improve neurological function and survival. In this study, we explore the hypothesis that administration of AAVrh.10hCLN2 to the neonatal brain will significantly improve the results of AAVrh.10hCLN2 therapy. To assess this concept, AAVrh.10hCLN2 vector was administered directly to the CNS of CLN2 knockout mice at 2 days, 3 wk and 7 wk of age. While all treatment groups show a marked increase in total TPP-I activity over wild-type mice, neonatally treated mice displayed high levels of TPP-I activity in the CNS 1 yr after administration which was spread throughout the brain. Using behavioral markers, 2 day-treated mice demonstrate marked improvement over 3 wk, 7 wk or untreated mice. Finally, neonatal administration of AAVrh.10hCLN2 was associated with markedly enhanced survival, with a median time of death 376 days for neonatal treated mice, 277 days for 3 wk-treated mice, 168 days for 7 wk-treated mice, and 121 days for untreated mice. These data suggest that neonatal treatment offers many unique advantages, and that early detection and treatment may be essential for maximal gene therapy for childhood lysosomal storage disorders affecting the CNS.
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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.