ArticleMolecular genetics and metabolism2008
Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis.
Article in Molecular genetics and metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Dose selection for intracerebroventricular cerliponase alfa in children with CLN2 disease, translation from animal to human in a rare genetic disease.Clinical and translational science · 2021Trial
- Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration.Clinical and translational science · 2021Trial
- PPARα and RXRα in the regulation of neuronal ceroid lipofuscinosis genes: implications for Batten disease therapy.NeuroImmune pharmacology and therapeutics · 2026Article
- Article
- A Novel Porcine Model of CLN2 Batten Disease that Recapitulates Patient Phenotypes.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Retinal degeneration in mice and humans with neuronal ceroid lipofuscinosis type 8.Annals of translational medicine · 2021Article
- Effect of small molecule eRF3 degraders on premature termination codon readthrough.Nucleic acids research · 2021Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Analysis of Brain and Cerebrospinal Fluid from Mouse Models of the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Changes in the Lysosomal Proteome.Molecular & cellular proteomics : MCP · 2019Article
- 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
- Inducible transgenic expression of tripeptidyl peptidase 1 in a mouse model of late-infantile neuronal ceroid lipofuscinosis.PloS one · 2018Article
- A Basic ApoE-Based Peptide Mediator to Deliver Proteins across the Blood-Brain Barrier: Long-Term Efficacy, Toxicity, and Mechanism.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Gemfibrozil, food and drug administration-approved lipid-lowering drug, increases longevity in mouse model of late infantile neuronal ceroid lipofuscinosis.Journal of neurochemistry · 2017Article
- 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
- A tailored mouse model of CLN2 disease: A nonsense mutant for testing personalized therapies.PloS one · 2017Article
- Novel small molecules potentiate premature termination codon readthrough by aminoglycosides.Nucleic acids research · 2016Article
- Gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, up-regulate tripeptidyl-peptidase 1 in brain cells via peroxisome proliferator-activated receptor α: implications for late infantile Batten disease therapy.The Journal of biological chemistry · 2012Article
- Article
- Large-volume intrathecal enzyme delivery increases survival of a mouse model of late infantile neuronal ceroid lipofuscinosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
- Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses.Current pharmaceutical biotechnology · 2011Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a hereditary neurodegenerative disease of childhood that is caused by mutations in the gene (CLN2) encoding the lysosomal protease tripeptidyl-peptidase I (TPPI). LINCL is fatal and there is no treatment of demonstrated efficacy in affected children but preclinical studies with AAV-mediated gene therapy have demonstrated promise in a mouse model. Here, we have generated mouse CLN2-mutants that express different amounts of TPPI activity to benchmark levels required for therapeutic benefits. Approximately 3% of normal TPPI activity in brain delayed disease onset and doubled lifespan to a median of approximately 9 months compared to mice expressing approximately 0.2% of normal levels. Expression of 6% of normal TPPI activity dramatically attenuated disease, with a median lifespan of approximately 20 months which approaches that of unaffected mice. While the lifespan of this hypomorph is shortened, disease is late-onset, less severe and progresses slowly compared to mice expressing lower TPPI levels. For gene therapy and other approaches that restore enzyme activity, these results suggest that 6% of normal TPPI activity throughout the CNS of affected individuals will provide a significant therapeutic benefit but higher levels will be required to cure this disease.
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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.