ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Liver production of sulfamidase reverses peripheral and ameliorates CNS pathology in mucopolysaccharidosis IIIA mice.
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 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- AAV-mediated delivery of secreted acid α-glucosidase with enhanced uptake corrects neuromuscular pathology in Pompe mice.JCI insight · 2023Article
- Engineered AAV8 capsid acquires heparin and AVB sepharose binding capacity but has altered in vivo transduction efficiency.Gene therapy · 2023Article
- Mucopolysaccharidoses and the blood-brain barrier.Fluids and barriers of the CNS · 2022Review
- AAV-mediated BMP7 gene therapy counteracts insulin resistance and obesity.Molecular therapy. Methods & clinical development · 2022Article
- Delivering gene therapy for mucopolysaccharide diseases.Frontiers in molecular biosciences · 2022Review
- Impaired neural differentiation of MPS IIIA patient induced pluripotent stem cell-derived neural progenitor cells.Molecular genetics and metabolism reports · 2021Article
- Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates.Nature communications · 2021Article
- A novel therapeutic strategy for skeletal disorders: Proof of concept of gene therapy for X-linked hypophosphatemia.Science advances · 2021Article
- Treatment of skeletal and non-skeletal alterations of Mucopolysaccharidosis type IVA by AAV-mediated gene therapy.Nature communications · 2021Article
- Novel therapies for mucopolysaccharidosis type III.Journal of inherited metabolic disease · 2021Review
- Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches.International journal of molecular sciences · 2020Review
- Rescue of Advanced Pompe Disease in Mice with Hepatic Expression of Secretable Acid α-Glucosidase.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Intravenous delivery of a chemically modified sulfamidase efficiently reduces heparan sulfate storage and brain pathology in mucopolysaccharidosis IIIA mice.Molecular genetics and metabolism reports · 2019Article
- Rescue of GSDIII Phenotype with Gene Transfer Requires Liver- and Muscle-Targeted GDE Expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Gene therapy for Mucopolysaccharidoses.Molecular genetics and metabolism · 2018Review
- Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase.Science translational medicine · 2017Article
- Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III.Orphanet journal of rare diseases · 2017Article
- Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC.Disease models & mechanisms · 2016Article
- CNS-directed gene therapy for the treatment of neurologic and somatic mucopolysaccharidosis type II (Hunter syndrome).JCI insight · 2016Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucopolysaccharidosis type IIIA (MPSIIIA) is an inherited lysosomal storage disease caused by deficiency of sulfamidase, resulting in accumulation of the glycosaminoglycan (GAG) heparan sulfate. It is characterized by severe progressive neurodegeneration, together with somatic alterations, which lead to death during adolescence. Here, we tested the ability of adeno-associated virus (AAV) vector-mediated genetic modification of either skeletal muscle or liver to revert the already established disease phenotype of 2-month-old MPSIIIA males and females. Intramuscular administration of AAV-Sulfamidase failed to achieve significant therapeutic benefit in either gender. In contrast, AAV8-mediated liver-directed gene transfer achieved high and sustained levels of circulating active sulfamidase, which reached normal levels in females and was fourfold higher in males, and completely corrected lysosomal GAG accumulation in most somatic tissues. Remarkably, a 50% reduction of GAG accumulation was achieved throughout the entire brain of males, which correlated with a partial improvement of the pathology of cerebellum and cortex. Liver-directed gene transfer expanded the lifespan of MPSIIIA males, underscoring the importance of reaching supraphysiological plasma levels of enzyme for maximal therapeutic benefit. These results show how liver-directed gene transfer can reverse somatic and ameliorate neurological pathology in MPSIIIA.
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