ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Longitudinal In Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 94 citations in OpenAlex.
- Translational lipidomics reveals BMP and its precursor LPG as biomarkers for CLN5 Batten disease.bioRxiv : the preprint server for biology · 2026Article
- 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
- Magnetic Resonance Imaging as a Readout of CLN5 Gene Therapy Efficacy in Sheep.Brain and behavior · 2025Article
- Evaluation of neuroretina following i.v. or intra-CSF AAV9 gene replacement in mice with MPS IIIA, a childhood dementia.CNS neuroscience & therapeutics · 2024Article
- Neurosurgical gene therapy for central nervous system diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Toward the "Perfect" Shunt: Historical Vignette, Current Efforts, and Future Directions.Advances and technical standards in neurosurgery · 2024Article
- A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes.Disease models & mechanisms · 2023Article
- Intraparenchymal convection enhanced delivery of AAV in sheep to treat Mucopolysaccharidosis IIIC.Journal of translational medicine · 2023Article
- Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model.Scientific reports · 2023Article
- Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease.Frontiers in genetics · 2023Article
- Efficacy of dual intracerebroventricular and intravitrealFrontiers in pharmacology · 2023Article
- Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease.Frontiers in genetics · 2023Article
- Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis.Brain communications · 2023Article
- [Application of adeno-associated virus-mediated gene therapy in lysosomal storage diseases].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Review
- Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep.The Journal of clinical investigation · 2022Article
- A Novel Porcine Model of CLN2 Batten Disease that Recapitulates Patient Phenotypes.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Modelling Neurological Diseases in Large Animals: Criteria for Model Selection and Clinical Assessment.Cells · 2022Review
- The Sheep as a Large Animal Model for the Investigation and Treatment of Human Disorders.Biology · 2022Review
- Ocular therapies for neuronal ceroid lipofuscinoses: more than meets the eye.Neural regeneration research · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are neurodegenerative lysosomal storage diseases predominantly affecting children. Single administration of brain-directed lentiviral or recombinant single-stranded adeno-associated virus 9 (ssAAV9) vectors expressing ovine CLN5 into six pre-clinically affected sheep with a naturally occurring CLN5 NCL resulted in long-term disease attenuation. Treatment efficacy was demonstrated by non-invasive longitudinal in vivo monitoring developed to align with assessments used in human medicine. The treated sheep retained neurological and cognitive function, and one ssAAV9-treated animal has been retained and is now 57 months old, almost triple the lifespan of untreated CLN5-affected sheep. The onset of visual deficits was much delayed. Computed tomography and MRI showed that brain structures and volumes remained stable. Because gene therapy in humans is more likely to begin after clinical diagnosis, self-complementary AAV9-CLN5 was injected into the brain ventricles of four 7-month-old affected sheep already showing early clinical signs in a second trial. This also halted disease progression beyond their natural lifespan. These findings demonstrate the efficacy of CLN5 gene therapy, using three different vector platforms, in a large animal model and, thus, the prognosis for human translation.
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