ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Normalization and improvement of CNS deficits in mice with Hurler syndrome after long-term peripheral delivery of BBB-targeted iduronidase.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- 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
- Ready-to-use iPSC-derived microglia progenitors for the treatment of CNS disease in mouse models of neuropathic mucopolysaccharidoses.Nature communications · 2024Article
- Embryo and fetal gene editing: Technical challenges and progress toward clinical applications.Molecular therapy. Methods & clinical development · 2024Review
- Liver-directed gene therapy corrects neurologic disease in a murine model of mucopolysaccharidosis type I-Hurler.Molecular therapy. Methods & clinical development · 2022Article
- Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement.Biomolecules · 2021Review
- miR-143 Regulates Lysosomal Enzyme Transport across the Blood-Brain Barrier and Transforms CNS Treatment for Mucopolysaccharidosis Type I.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Hurdles in treating Hurler disease: potential routes to achieve a "real" cure.Blood advances · 2020Review
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Getting the Most: Enhancing Efficacy by Promoting Erythropoiesis and Thrombopoiesis after Gene Therapy in Mice with Hurler Syndrome.Molecular therapy. Methods & clinical development · 2018Article
- Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.EMBO molecular medicine · 2018Article
- Transcranial pulsed ultrasound facilitates brain uptake of laronidase in enzyme replacement therapy for Mucopolysaccharidosis type I disease.Orphanet journal of rare diseases · 2017Article
- Hematopoietic Stem cell transplantation and lentiviral vector-based gene therapy for Krabbe's disease: Present convictions and future prospects.Journal of neuroscience research · 2016Article
- Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease.PloS one · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mucopolysaccharidosis type I (MPS I) is a progressive lysosomal storage disorder with systemic and central nervous system (CNS) involvement due to deficiency of α-L-iduronidase (IDUA). We previously identified a receptor-binding peptide from apolipoprotein E (e) that facilitated a widespread delivery of IDUAe fusion protein into CNS. In this study, we evaluated the long-term CNS biodistribution, dose-correlation, and therapeutic benefits of IDUAe after systemic, sustained delivery via hematopoietic stem cell (HSC)-mediated gene therapy with expression restricted to erythroid/megakaryocyte lineages. Compared to the highest dosage group treated by nontargeted control IDUAc (165 U/ml), physiological levels of IDUAe in the circulation (12 U/ml) led to better CNS benefits in MPS I mice as demonstrated in glycosaminoglycan accumulation, histopathology analysis, and neurological behavior. Long-term brain metabolic correction and normalization of exploratory behavior deficits in MPS I mice were observed by peripheral enzyme therapy with physiological levels of IDUAe derived from clinically attainable levels of HSC transduction efficiency (0.1). Importantly, these levels of IDUAe proved to be more beneficial on correction of cerebrum pathology and behavioral deficits in MPS I mice than wild-type HSCs fully engrafted in MPS I chimeras. These results provide compelling evidence for CNS efficacy of IDUAe and its prospective translation to clinical application.
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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.