ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Large-volume intrathecal enzyme delivery increases survival of a mouse model of late infantile neuronal ceroid lipofuscinosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- PPARα and RXRα in the regulation of neuronal ceroid lipofuscinosis genes: implications for Batten disease therapy.NeuroImmune pharmacology and therapeutics · 2026Article
- Elevated tripeptidyl-peptidase 1 corrects multiple disease phenotypes in a mouse model of juvenile neuronal ceroid lipofuscinosis.Molecular therapy. Methods & clinical development · 2025Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- A mouse mutant deficient in both neuronal ceroid lipofuscinosis-associated proteins CLN3 and TPP1.Journal of inherited metabolic disease · 2023Article
- A mechanistic pharmacokinetic model for intrathecal administration of antisense oligonucleotides.Frontiers in physiology · 2023Article
- Brain transcriptome analysis of a CLN2 mouse model as a function of disease progression.Journal of neuroinflammation · 2021Article
- Patient-Derived Induced Pluripotent Stem Cell Models for Phenotypic Screening in the Neuronal Ceroid Lipofuscinoses.Molecules (Basel, Switzerland) · 2021Review
- Exploiting the diphtheria toxin internalization receptor enhances delivery of proteins to lysosomes for enzyme replacement therapy.Science advances · 2020Article
- Lysosomal protein thermal stability does not correlate with cellular half-life: global observations and a case study of tripeptidyl-peptidase 1.The Biochemical journal · 2020Article
- 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
- Cell and Gene Therapies for Mucopolysaccharidoses: Base Editing and Therapeutic Delivery to the CNS.Diseases (Basel, Switzerland) · 2019Review
- Routes for the delivery of insulin to the central nervous system: A comparative review.Experimental neurology · 2019Review
- 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
- Flupirtine derivatives as potential treatment for the neuronal ceroid lipofuscinoses.Annals of clinical and translational neurology · 2018Article
- Inducible transgenic expression of tripeptidyl peptidase 1 in a mouse model of late-infantile neuronal ceroid lipofuscinosis.PloS one · 2018Article
- Proteomic Analysis of Brain and Cerebrospinal Fluid from the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Potential Biomarkers.Journal of proteome research · 2017Article
- 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
- 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
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Late infantile neuronal ceroid lipofuscinosis (LINCL) is a progressive neurodegenerative lysosomal storage disorder caused by mutations in TPP1, the gene encoding the lysosomal protease tripeptidyl-peptidase (TPP1). LINCL primarily affects children, is fatal and there is no effective treatment. Administration of recombinant protein has proved effective in treatment of visceral manifestations of other lysosomal storage disorders but to date, only marginal improvement in survival has been obtained for neurological diseases. In this study, we have developed and optimized a large-volume intrathecal administration strategy to deliver therapeutic amounts of TPP1 to the central nervous system (CNS) of a mouse model of LINCL. To determine the efficacy of treatment, we have monitored survival as the primary endpoint and demonstrate that an acute treatment regimen (three consecutive daily doses started at 4 weeks of age) increases median lifespan of the LINCL mice from 16 (vehicle treated) to 23 weeks (enzyme treated). Consistent with the increase in life-span, we also observed significant reversal of pathology and improvement in neurological phenotype. These results provide a strong basis for both clinical investigation of large-volume/high-dose delivery of TPP1 to the brain via the cerebrospinal fluid (CSF) and extension of this approach towards other neurological lysosomal storage diseases.
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