ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Broad functional correction of molecular impairments by systemic delivery of scAAVrh74-hSGSH gene delivery in MPS IIIA mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.International journal of molecular sciences · 2024Review
- Paving the way for future gene therapies: A case study of scientific spillover from delandistrogene moxeparvovec.Molecular therapy. Methods & clinical development · 2023Review
- Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy.International journal of molecular sciences · 2022Review
- Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art.International journal of molecular sciences · 2021Review
- Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development.Biomolecules · 2021Review
- Genetic testing of Mucopolysaccharidoses disease using multiplex PCR- based panels of STR markers: in silico analysis of novel mutations.Metabolic brain disease · 2019Article
- Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy.Human gene therapy. Clinical development · 2017Article
- Serum global metabolomics profiling reveals profound metabolic impairments in patients with MPS IIIA and MPS IIIB.Metabolic brain disease · 2017Article
- In Vivo Genome Editing Restores Dystrophin Expression and Cardiac Function in Dystrophic Mice.Circulation research · 2017Article
- Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3).The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC.Disease models & mechanisms · 2016Article
- Adeno-Associated Virus-Based Gene Therapy for CNS Diseases.Human gene therapy · 2016Review
- A Comprehensive Map of CNS Transduction by Eight Recombinant Adeno-associated Virus Serotypes Upon Cerebrospinal Fluid Administration in Pigs.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Transplantation of Wild-Type Hematopoietic Stem and Progenitor Cells Improves Disease Phenotypes in a Mucopolysaccharidosis IIIC Mouse Model.Cell transplantationArticle
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Authors and funding
10 authors at 1 institution in 1 country.
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Abstract
Mucopolysaccharidosis (MPS) IIIA is a neuropathic lysosomal storage disease caused by deficiency in N-sulfoglucosamine sulfohydrolase (SGSH). Genome-wide gene expression microarrays in MPS IIIA mice detected broad molecular abnormalities (greater than or equal to twofold, false discovery rate ≤10) in numerous transcripts (314) in the brain and blood (397). Importantly, 22 dysregulated blood transcripts are known to be enriched in the brain and linked to broad neuronal functions. To target the root cause, we used a self-complementary AAVrh74 vector to deliver the human SGSH gene into 4-6 weeks old MPS IIIA mice by an intravenous injection. The treatment resulted in global central nervous system (CNS) and widespread somatic restoration of SGSH activity, clearance of CNS and somatic glycosaminoglycan storage, improved behavior performance, and significantly extended survival. The scAAVrh74-hSGSH treatment also led to the correction of the majority of the transcriptional abnormalities in the brain (95.9%) and blood (97.7%), of which 182 and 290 transcripts were normalized in the brain and blood, respectively. These results demonstrate that a single systemic scAAVrh74-hSGSH delivery mediated efficient restoration of SGSH activity and resulted in a near complete correction of MPS IIIA molecular pathology. This study also demonstrates that blood transcriptional profiles reflect the biopathological status of MPS IIIA, and also respond well to effective treatments.
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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.