ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
An anti-neuroinflammatory that targets dysregulated glia enhances the efficacy of CNS-directed gene therapy in murine infantile neuronal ceroid lipofuscinosis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- Systemic AAV9 Gene Therapy Mitigates Neuromuscular Junction Degeneration and Muscle Atrophy in a Mouse Model of CLN1 Disease.International journal of molecular sciences · 2026Article
- Enteric nervous system degeneration in human and murine CLN3 disease, is ameliorated by gene therapy in mice.Acta neuropathologica communications · 2025Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- Gene therapy ameliorates neuromuscular pathology in CLN3 disease.Acta neuropathologica communications · 2025Article
- Neuronal Ceroid Lipofuscinosis-Concepts, Classification, and Avenues for Therapy.CNS neuroscience & therapeutics · 2025Review
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Characterization of early markers of disease in the mouse model of mucopolysaccharidosis IIIB.Journal of neurodevelopmental disorders · 2024Article
- Akap5 links synaptic dysfunction to neuroinflammatory signaling in a mouse model of infantile neuronal ceroid lipofuscinosis.Frontiers in synaptic neuroscience · 2024Article
- ILAE Genetics Literacy series: Progressive myoclonus epilepsies.Epileptic disorders : international epilepsy journal with videotape · 2023Review
- An innovative hematopoietic stem cell gene therapy approach benefits CLN1 disease in the mouse model.EMBO molecular medicine · 2023Article
- Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures.Scientific reports · 2022Article
- Seizures in PPT1 Knock-In Mice Are Associated with Inflammatory Activation of Microglia.International journal of molecular sciences · 2022Article
- Characterization of neurological disease progression in a canine model of CLN5 neuronal ceroid lipofuscinosis.Developmental neurobiology · 2022Article
- Application of Anticonvulsants, Antiepileptic Drugs, and Vitamin C in the Treatment and Analysis of Batten Disease.Cureus · 2022Review
- Article
- Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview.Frontiers in neurology · 2022Review
- Glial Dysfunction and Its Contribution to the Pathogenesis of the Neuronal Ceroid Lipofuscinoses.Frontiers in neurology · 2022Review
- Experimental Therapeutic Approaches for the Treatment of Retinal Pathology in Neuronal Ceroid Lipofuscinoses.Frontiers in neurology · 2022Review
- Spinal manifestations of CLN1 disease start during the early postnatal period.Neuropathology and applied neurobiology · 2021Article
- [Neuroinflammation in neuronal ceroid lipofuscinosis].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2021Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited neurodegenerative lysosomal storage disease (LSD) caused by a deficiency in palmitoyl protein thioesterase-1 (PPT1). Studies in Ppt1(-/-) mice demonstrate that glial activation is central to the pathogenesis of INCL. Astrocyte activation precedes neuronal loss, while cytokine upregulation associated with microglial reactivity occurs before and concurrent with neurodegeneration. Therefore, we hypothesized that cytokine cascades associated with neuroinflammation are important therapeutic targets for the treatment of INCL. MW01-2-151SRM (MW151) is a blood-brain barrier penetrant, small-molecule anti-neuroinflammatory that attenuates glial cytokine upregulation in models of neuroinflammation such as traumatic brain injury, Alzheimer's disease, and kainic acid toxicity. Thus, we used MW151, alone and in combination with CNS-directed, AAV-mediated gene therapy, as a possible treatment for INCL. MW151 alone decreased seizure susceptibility. When combined with AAV-mediated gene therapy, treated INCL mice had increased life spans, improved motor performance, and eradication of seizures. Combination-treated INCL mice also had decreased brain atrophy, astrocytosis, and microglial activation, as well as intermediary effects on cytokine upregulation. These data suggest that MW151 can attenuate seizure susceptibility but is most effective when used in conjunction with a therapy that targets the primary genetic defect.
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