ArticleGene therapy2015
Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease.
Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 78 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
- Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025Review
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- 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 AAV-mediated gene replacement therapy for pediatric monogenic neurological disorders.Molecular therapy. Methods & clinical development · 2024Review
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Intrathecal delivery of a bicistronic AAV9 vector expressing β-hexosaminidase A corrects Sandhoff disease in a murine model: A dosage study.Molecular therapy. Methods & clinical development · 2024Article
- Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy.Annals of neurology · 2023Article
- Gene Therapy of Sphingolipid Metabolic Disorders.International journal of molecular sciences · 2023Review
- Therapeutic advantages of combined gene/cell therapy strategies in a murine model of GM2 gangliosidosis.Molecular therapy. Methods & clinical development · 2022Article
- AAV gene therapy for Tay-Sachs disease.Nature medicine · 2022Article
- The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment.Neuroscience letters · 2021Article
- Adeno-Associated Vector-Delivered CRISPR/Viruses · 2021Article
- Magnetic resonance imaging and spectroscopy in late-onset GM2-gangliosidosis.Molecular genetics and metabolism · 2021Article
- Therapeutic benefit after intracranial gene therapy delivered during the symptomatic stage in a feline model of Sandhoff disease.Gene therapy · 2021Article
- Rapid Identification of New Biomarkers for the Classification of GM1 Type 2 Gangliosidosis Using an UnbiasedCells · 2021Article
- White Matter Pathology as a Barrier to Gangliosidosis Gene Therapy.Frontiers in cellular neuroscience · 2021Review
- Genoarchitectonic Compartmentalization of the Embryonic Telencephalon: Insights From the Domestic Cat.Frontiers in neuroanatomy · 2021Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Sandhoff disease (SD) is caused by deficiency of N-acetyl-β-hexosaminidase (Hex) resulting in pathological accumulation of GM2 ganglioside in lysosomes of the central nervous system (CNS) and progressive neurodegeneration. Currently, there is no treatment for SD, which often results in death by the age of five years. Adeno-associated virus (AAV) gene therapy achieved global CNS Hex restoration and widespread normalization of storage in the SD mouse model. Using a similar treatment approach, we sought to translate the outcome in mice to the feline SD model as an important step toward human clinical trials. Sixteen weeks after four intracranial injections of AAVrh8 vectors, Hex activity was restored to above normal levels throughout the entire CNS and in cerebrospinal fluid, despite a humoral immune response to the vector. In accordance with significant normalization of a secondary lysosomal biomarker, ganglioside storage was substantially improved, but not completely cleared. At the study endpoint, 5-month-old AAV-treated SD cats had preserved neurological function and gait compared with untreated animals (humane endpoint, 4.4±0.6 months) demonstrating clinical benefit from AAV treatment. Translation of widespread biochemical disease correction from the mouse to the feline SD model provides optimism for treatment of the larger human CNS with minimal modification of approach.
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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.