ArticleMolecular genetics and metabolism2014
High-dose enzyme replacement therapy in murine Hurler syndrome.
Article in Molecular genetics and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
- Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment.Molecular genetics and metabolismTrial
- CSF GAG non-reducing ends in MPS IH after peripheral and brain-penetrating therapies: A model comparing IV non-targeted ERT and HCT.Molecular therapy. Advances · 2026Article
- 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
- Intrathecal or intravenous AAV9-IDUA/RGX-111 at minimal effective dose prevents cardiac, skeletal and neurologic manifestations of murine MPS I.Molecular therapy. Methods & clinical development · 2024Article
- Engineering memory T cells as a platform for long-term enzyme replacement therapy in lysosomal storage disorders.Molecular therapy : the journal of the American Society of 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
- Efficacy of a Combination Therapy with Laronidase and Genistein in Treating Mucopolysaccharidosis Type I in a Mouse Model.International journal of molecular sciences · 2024Article
- Mapping brain networks in MPS I mice and their restoration following gene therapy.Scientific reports · 2023Article
- Targeting the central nervous system in lysosomal storage diseases: Strategies to deliver therapeutics across the blood-brain barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Non-invasive intravenous administration of AAV9 transducing iduronate sulfatase leads to global metabolic correction and prevention of neurologic deficits in a mouse model of Hunter syndrome.Molecular genetics and metabolism reports · 2023Article
- Liver-directed gene therapy corrects neurologic disease in a murine model of mucopolysaccharidosis type I-Hurler.Molecular therapy. Methods & clinical development · 2022Article
- Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I.Molecular genetics and metabolism · 2022Article
- Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Examination of a blood-brain barrier targeting β-galactosidase-monoclonal antibody fusion protein in a murine model of GM1-gangliosidosis.Molecular genetics and metabolism reports · 2021Article
- Comparative Effectiveness of Intracerebroventricular, Intrathecal, and Intranasal Routes of AAV9 Vector Administration for Genetic Therapy of Neurologic Disease in Murine Mucopolysaccharidosis Type I.Frontiers in molecular neuroscience · 2021Article
- Intravenous delivery for treatment of mucopolysaccharidosis type I: A comparison of AAV serotypes 9 and rh10.Molecular genetics and metabolism reports · 2020Article
- A Highly Efficacious PS Gene Editing System Corrects Metabolic and Neurological Complications of Mucopolysaccharidosis Type I.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- A novel gene editing system to treat both Tay-Sachs and Sandhoff diseases.Gene therapy · 2020Article
- Article
- Targeting Macromolecules to CNS and Other Hard-to-Treat Organs Using Lectin-Mediated Delivery.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease that is systemic, including progressive neurodegeneration, mental retardation and death before the age of 10 years. MPS I results from deficiency of α-L-iduronidase (IDUA) in lysosomes and subsequent accumulation of glycosaminoglycans (GAG). Clinical enzyme replacement therapy (ERT) with intravenous laronidase reverses some aspects of MPS I disease (e.g., hepatomegaly, splenomegaly, glycosaminoglycanuria) and ameliorates others (e.g., pulmonary function, cardiac disease, arthropathy, exercise tolerance). However, neurologic benefits are thought to be negligible because the blood-brain barrier (BBB) blocks enzyme from reaching the central nervous system (CNS). We considered the possibility that a very high dose of intravenous laronidase might be able to traverse the BBB in small quantities, and provide some metabolic correction in the brain. To address this question, high-dose laronidase was administered (11.6 mg/kg, once per week, 4 weeks) to adult MPS I mice. IDUA enzyme activity in the cortex of treated mice increased to 97% of that in wild type mice (p<0.01). GAG levels in cortex were reduced by 63% of that from untreated MPS I mice (p<0.05). Further, immunohistochemical analysis showed that treatment reduced secondary GM3-ganglioside accumulation in treated MPS I mice. Water T-maze tests showed that the learning abnormality in MPS I mice was reduced (p<0.0001). In summary, repeated, high-dose ERT facilitated laronidase transit across the BBB, reduced GAG accumulation within the CNS, and rescued cognitive impairment.
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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.