ArticleScience translational medicine2025
Gene therapy ameliorates bowel dysmotility and enteric neuron degeneration and extends survival in lysosomal storage disorder mouse models.
Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Gut-Brain Interactions in Neuronal Ceroid Lipofuscinoses: A Systematic Review Beyond the Brain in Paediatric Dementias.International journal of molecular sciences · 2025Pooled it
- Fusobacterium nucleatum enhances enterotoxigenic Bacteroides fragilis-mediated neuron loss and intestinal motility dysfunction.Nature microbiology · 2026Article
- Characterizing enteric pathology in MPS IIIA mice suggests disease-specific vulnerability among lysosomal storage disorders.JCI insight · 2026Article
- High-resolution promoter interaction analysis implicates genes involved in activation of type 3 innate lymphoid cells in immune disease risk.Nature genetics · 2026Article
- Enteric nervous system disease in neuronopathic lysosomal storage disorders.Neural regeneration research · 2026Article
- Antibiotic treatment reveals the contributions of the gut microbiome to CLN2 disease in the central and enteric nervous system.Scientific reports · 2026Article
- Systemic AAV9 Gene Therapy Mitigates Neuromuscular Junction Degeneration and Muscle Atrophy in a Mouse Model of CLN1 Disease.International journal of molecular sciences · 2026Article
- High-resolution promoter interaction analysis implicates genes involved in the activation of Type 3 Innate Lymphoid Cells in autoimmune disease risk.bioRxiv : the preprint server for biology · 2026Article
- Chronic oral cannabidiol delays seizure onset and reduces seizure burden in a mouse model of CLN2 disease.PloS one · 2026Article
- Limited therapeutic efficacy of N-acetyl-L-leucine in a mouse model of CLN1 disease.Scientific reports · 2025Article
- Enteric nervous system degeneration in human and murine CLN3 disease, is ameliorated by gene therapy in mice.Acta neuropathologica communications · 2025Article
- Gastrointestinal symptoms in neuronal ceroid lipofuscinoses (NCLs): an observational study on prevalence, timing of progression, and impact on quality of life.Neurogenetics · 2025Observational
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- AAV-delivered PPT1 provides long-term neurological benefits in CLN1 mice and achieves therapeutic levels in sheep brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene therapy ameliorates neuromuscular pathology in CLN3 disease.Acta neuropathologica communications · 2025Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Children with neurodegenerative disease often have debilitating gastrointestinal symptoms. We hypothesized that this may be due at least in part to underappreciated degeneration of neurons in the enteric nervous system (ENS), the master regulator of bowel function. To test this hypothesis, we evaluated mouse models of neuronal ceroid lipofuscinosis type 1 and 2 (CLN1 and CLN2 disease, respectively), neurodegenerative lysosomal storage disorders caused by deficiencies in palmitoyl protein thioesterase-1 and tripeptidyl peptidase-1, respectively. Both mouse lines displayed slow bowel transit in vivo that worsened with age. Although the ENS appeared to develop normally in these mice, there was a progressive and profound loss of myenteric plexus neurons accompanied by changes in enteric glia in adult mice. Similar pathology was evident in colon autopsy material from a child with CLN1 disease. Neonatal administration of adeno-associated virus-mediated gene therapy prevented bowel transit defects, ameliorated loss of enteric neurons, and extended survival in mice. Treatment after weaning was less effective than treating neonatally but still extended the lifespan of CLN1 disease mice. These data provide proof-of-principle evidence of ENS degeneration in two lysosomal storage diseases and suggest that gene therapy can ameliorate ENS disease, also improving survival.
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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.