ArticleScience translational medicine2015
AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 136 citations in OpenAlex.
- Slowing late infantile Batten disease by direct brain parenchymal administration of a rh.10 adeno-associated virus expressingScience translational medicine · 2020Trial
- Intra-CNS AAV9-Molecular therapy. Advances · 2026Article
- CAR-T cell therapy: potential for paediatric brain tumours-an update.Journal of neuro-oncology · 2026Review
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- CAR T-cell immunotherapy as the next horizon in cancer eradication: current landscape, challenges, and future directions.Medical oncology (Northwood, London, England) · 2025Review
- Intracisternal vs intraventricular injection of AAV1 result in comparable, widespread transduction of the dog brain.Gene therapy · 2025Article
- Endothelial and neuronal engagement by AAV-BR1 gene therapy alleviates neurological symptoms and lipid deposition in a mouse model of Niemann-Pick type C2.Fluids and barriers of the CNS · 2025Article
- Ependymal cells: roles in central nervous system infections and therapeutic application.Journal of neuroinflammation · 2024Review
- Evaluation of neuroretina following i.v. or intra-CSF AAV9 gene replacement in mice with MPS IIIA, a childhood dementia.CNS neuroscience & therapeutics · 2024Article
- Widespread correction of brain pathology in feline alpha-mannosidosis by dose escalation of intracisternal AAV vector injection.Molecular therapy. Methods & clinical development · 2024Article
- APOE2 gene therapy reduces amyloid deposition and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy.Annals of neurology · 2023Article
- Article
- A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes.Disease models & mechanisms · 2023Article
- A mouse mutant deficient in both neuronal ceroid lipofuscinosis-associated proteins CLN3 and TPP1.Journal of inherited metabolic disease · 2023Article
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Article
- Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model.Scientific reports · 2023Article
- Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease.Frontiers in genetics · 2023Article
- Intravitreal gene therapy preserves retinal function in a canine model of CLN2 neuronal ceroid lipofuscinosis.Experimental eye research · 2023Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The most common form of the childhood neurodegenerative disease late infantile neuronal ceroid lipofuscinosis (also called Batten disease) is caused by deficiency of the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1) resulting from mutations in the TPP1 gene. We tested whether TPP1 gene transfer to the ependyma, the epithelial lining of the brain ventricular system, in TPP1-deficient dogs would be therapeutically beneficial. A one-time administration of recombinant adeno-associated virus (rAAV) expressing canine TPP1 (rAAV.caTPP1) resulted in high expression of TPP1 predominantly in ependymal cells and secretion of the enzyme into the cerebrospinal fluid leading to clinical benefit. Diseased dogs treated with rAAV.caTPP1 showed delays in onset of clinical signs and disease progression, protection from cognitive decline, and extension of life span. By immunostaining and enzyme assay, recombinant protein was evident throughout the brain and spinal cord, with correction of the neuropathology characteristic of the disease. This study in a naturally occurring canine model of TPP1 deficiency highlights the utility of AAV transduction of ventricular lining cells to accomplish stable secretion of recombinant protein for broad distribution in the central nervous system and therapeutic benefit.
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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.