ArticleMolecular therapy. Methods & clinical development2020
7T MRI Predicts Amelioration of Neurodegeneration in the Brain after AAV Gene Therapy.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- AAV9 Gene Therapy in Type II GM1 Gangliosidosis - A Phase 1-2 Trial.The New England journal of medicine · 2026Trial
- Expanded Access use of Intravenous Gene Transfer with AAV9-GLB1 in a Juvenile GM1 Gangliosidosis Participant.medRxiv : the preprint server for health sciences · 2026Article
- A Case for Automated Segmentation of MRI Data in Neurodegenerative Diseases: Type II GM1 Gangliosidosis.NeuroSci · 2025Article
- Magnetic Resonance Imaging as a Readout of CLN5 Gene Therapy Efficacy in Sheep.Brain and behavior · 2025Article
- Differential tractography: an imaging marker for tissue degeneration in neurodegenerative diseases.Brain communications · 2025Article
- Therapeutic developments for neurodegenerative GM1 gangliosidosis.Frontiers in neuroscience · 2024Review
- Review
- Going beyond established model systems of Alzheimer's disease: companion animals provide novel insights into the neurobiology of aging.Communications biology · 2023Review
- A pentasaccharide for monitoring pharmacodynamic response to gene therapy in GM1 gangliosidosis.EBioMedicine · 2023Article
- Review
- Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- AAVrh10 vector corrects pathology in animal models of GM1 gangliosidosis and achieves widespread distribution in the CNS of nonhuman primates.Molecular therapy. Methods & clinical development · 2022Article
- Hematopoietic stem cell gene therapy ameliorates CNS involvement in murine model of GM1-gangliosidosis.Molecular therapy. Methods & clinical development · 2022Article
- Safety of Direct Intraparenchymal AAVrh.10-Mediated Central Nervous System Gene Therapy for Metachromatic Leukodystrophy.Human gene therapy · 2021Article
- GM1 Gangliosidosis: Mechanisms and Management.The application of clinical genetics · 2021Review
- White Matter Pathology as a Barrier to Gangliosidosis Gene Therapy.Frontiers in cellular neuroscience · 2021Review
- GM1 Gangliosidosis-A Mini-Review.Frontiers in genetics · 2021Review
- Natural history of Tay-Sachs disease in sheep.Molecular genetics and metabolismArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
GM1 gangliosidosis (GM1) is a fatal neurodegenerative lysosomal storage disease that occurs most commonly in young children, with no effective treatment available. Long-term follow-up of GM1 cats treated by bilateral thalamic and deep cerebellar nuclei (DCN) injection of adeno-associated virus (AAV)-mediated gene therapy has increased lifespan to 8 years of age, compared with an untreated lifespan of ~8 months. Due to risks associated with cerebellar injection in humans, the lateral ventricle was tested as a replacement route to deliver an AAVrh8 vector expressing feline β-galactosidase (β-gal), the defective enzyme in GM1. Treatment via the thalamus and lateral ventricle corrected storage, myelination, astrogliosis, and neuronal morphology in areas where β-gal was effectively delivered. Oligodendrocyte number increased, but only in areas where myelination was corrected. Reduced AAV and β-gal distribution were noted in the cerebellum with subsequent increases in storage, demyelination, astrogliosis, and neuronal degeneration. These postmortem findings were correlated with endpoint MRI and magnetic resonance spectroscopy (MRS). Compared with the moderate dose with which most cats were treated, a higher AAV dose produced superior survival, currently 6.5 years. Thus, MRI and MRS can predict therapeutic efficacy of AAV gene therapy and non-invasively monitor cellular events within the GM1 brain.
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What OpenQuestion holds
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.