ArticleNeuroscience2017
AAV-mediated gene delivery attenuates neuroinflammation in feline Sandhoff disease.
Article in Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
17 citing papers in PubMed, 31 citations in OpenAlex.
- Dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis: a phase 1/2 trial.Nature medicine · 2025Trial
- Cerebrospinal delivery of a bidirectional AAV9 vector improves optic nerve and retinal pathology in a sheep model of Tay-Sachs disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Age-sensitive response of systemic AAV-mediated gene therapy in a newly characterized feline model of mucolipidosis II.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Advances in Diagnosis, Pathological Mechanisms, Clinical Impact, and Future Therapeutic Perspectives in Tay-Sachs Disease.Neurology international · 2025Review
- Delivery of Adeno-Associated Virus Vectors to the Central Nervous System for Correction of Single Gene Disorders.International journal of molecular sciences · 2024Review
- The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment.Neuroscience letters · 2021Article
- Adeno-Associated Vector-Delivered CRISPR/Viruses · 2021Article
- Therapeutic benefit after intracranial gene therapy delivered during the symptomatic stage in a feline model of Sandhoff disease.Gene therapy · 2021Article
- White Matter Pathology as a Barrier to Gangliosidosis Gene Therapy.Frontiers in cellular neuroscience · 2021Review
- GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies.International journal of molecular sciences · 2020Review
- Adeno-associated virus-binding antibodies detected in cats living in the Northeastern United States lack neutralizing activity.Scientific reports · 2020Article
- 7T MRI Predicts Amelioration of Neurodegeneration in the Brain after AAV Gene Therapy.Molecular therapy. Methods & clinical development · 2020Article
- Brain endothelial specific gene therapy improves experimental Sandhoff disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Substrate Reduction Therapy for Sandhoff Disease through Inhibition of Glucosylceramide Synthase Activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Pre-existing antibodies to candidate gene therapy vectors (adeno-associated vector serotypes) in domestic cats.PloS one · 2019Article
- Natural history of Tay-Sachs disease in sheep.Molecular genetics and metabolismArticle
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Sandhoff disease (SD) is a lysosomal storage disorder characterized by the absence of hydrolytic enzyme β-N-acetylhexosaminidase (Hex), which results in storage of GM2 ganglioside in neurons and unremitting neurodegeneration. Neuron loss initially affects fine motor skills, but rapidly progresses to loss of all body faculties, a vegetative state, and death by five years of age in humans. A well-established feline model of SD allows characterization of the disease in a large animal model and provides a means to test the safety and efficacy of therapeutic interventions before initiating clinical trials. In this study, we demonstrate a robust central nervous system (CNS) inflammatory response in feline SD, primarily marked by expansion and activation of the microglial cell population. Quantification of major histocompatibility complex II (MHC-II) labeling revealed significant up-regulation throughout the CNS with areas rich in white matter most severely affected. Expression of the leukocyte chemokine macrophage inflammatory protein-1 alpha (MIP-1α) was also up-regulated in the brain. SD cats were treated with intracranial delivery of adeno-associated viral (AAV) vectors expressing feline Hex, with a study endpoint 16weeks post treatment. AAV-mediated gene delivery repressed the expansion and activation of microglia and normalized MHC-II and MIP-1α levels. These data reiterate the profound inflammatory response in SD and show that neuroinflammation is abrogated after AAV-mediated restoration of enzymatic activity.
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Registered trials
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.