ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. 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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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.
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Who cites it
44 citing papers in PubMed, 76 citations in OpenAlex.
- Review
- AAV-based gene therapy with modified HEXB confers lasting therapeutic benefits in GM2 gangliosidosis models.Cell reports. Medicine · 2026Article
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- Late-onset GM2 gangliosidosis: magnetic resonance imaging, diffusion tensor imaging, and correlational fiber tractography differentiate Tay-Sachs and Sandhoff diseases.Journal of neurology · 2025Article
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- Treating late-onset Tay Sachs disease: Brain delivery with a dual trojan horse protein.Molecular therapy. Methods & clinical development · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Targeting GM2 Ganglioside Accumulation in Dementia: Current Therapeutic Approaches and Future Directions.Current molecular medicine · 2024Review
- Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy.Annals of neurology · 2023Article
- Efficacy of Adeno-Associated Virus Serotype 9-Mediated Gene Therapy for AB-Variant GM2 Gangliosidosis.International journal of molecular sciences · 2023Article
- 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
- 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
- Pronounced Therapeutic Benefit of a Single Bidirectional AAV Vector Administered Systemically in Sandhoff Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Dual Purpose Vectors for Rare Neurological Diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies.International journal of molecular sciences · 2020Review
- 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 novel gene editing system to treat both Tay-Sachs and Sandhoff diseases.Gene therapy · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system.
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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.