ArticleEMBO molecular medicine2018
Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.
Article in EMBO molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 87 citations in OpenAlex.
- Mucopolysaccharidosis Type II Screening, Diagnosis, and Management: A Literature Review and Practical Recommendations for Newborn Screening Programs and Health Care Providers to Support Families and Improve Outcomes.International journal of neonatal screening · 2026Review
- Commentary: Lysosomal enzymes engineered to cross the blood-brain barrier are reshaping the therapeutic landscape of neuronopathic mucopolysaccharidoses.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Domain-substituted IGF2 tag modulates targeting of lentiviral gene therapy for Hunter syndrome.EMBO molecular medicine · 2025Article
- Rescue of neurologic disease in mucopolysaccharidosis type II mice via AAV-mediated liver delivery of brain-penetrating iduronate-2-sulfatase.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Designing better gene therapies for lysosomal storage disorders using engineered enzymes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Hematopoietic stem cell gene therapy of neurometabolic lysosomal storage diseases.Brain & development · 2025Review
- Clinical hematopoietic stem cell-based gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Oral trehalose improves histological and behavior symptoms of mucopolysaccharidosis type II in iduronate 2-sulfatase deficient mice.Scientific reports · 2025Article
- Preclinical lentiviral hematopoietic stem cell gene therapy corrects Pompe disease-related muscle and neurological manifestations.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Lentiviral Vector-MediatedHuman gene therapy · 2024Article
- Systemic immune challenge exacerbates neurodegeneration in a model of neurological lysosomal disease.EMBO molecular medicine · 2024Article
- Design and validation of a GMP stem cell manufacturing protocol for MPSII hematopoietic stem cell gene therapy.Molecular therapy. Methods & clinical development · 2024Article
- Lentiviral Gene Therapy for Mucopolysaccharidosis II with Tagged Iduronate 2-Sulfatase Prevents Life-Threatening Pathology in Peripheral Tissues But Fails to Correct Cartilage.Human gene therapy · 2024Article
- Comparative dose effectiveness of intravenous and intrathecal AAV9.CB7.hIDS, RGX-121, in mucopolysaccharidosis type II mice.Molecular therapy. Methods & clinical development · 2024Article
- An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Brain-targetedMolecular therapy. Methods & clinical development · 2023Article
- Tagged IDS causes efficient and engraftment-independent prevention of brain pathology during lentiviral gene therapy for Mucopolysaccharidosis type II.Molecular therapy. Methods & clinical development · 2023Article
- Sustained long-term disease correction in a murine model of MPSII following stem cell gene therapy.Molecular therapy. Methods & clinical development · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS.ApoEII) compared to a lentivirus expressing normal IDS or a normal bone marrow transplant. In mucopolysaccharidosis II mice, all treatments corrected peripheral disease, but only IDS.ApoEII mediated complete normalization of brain pathology and behavior, providing significantly enhanced correction compared to IDS. A normal bone marrow transplant achieved no brain correction. Whilst corrected macrophages traffic to the brain, secreting IDS/IDS.ApoEII enzyme for cross-correction, IDS.ApoEII was additionally more active in plasma and was taken up and transcytosed across brain endothelia significantly better than IDS via both heparan sulfate/ApoE-dependent receptors and mannose-6-phosphate receptors. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients.
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Registered trials
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