ArticlePloS one2012
CNS penetration of intrathecal-lumbar idursulfase in the monkey, dog and mouse: implications for neurological outcomes of lysosomal storage disorder.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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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
64 citing papers in PubMed, 140 citations in OpenAlex.
- Caregiver experiences and observations of intrathecal idursulfase-IT treatment in a phase 2/3 trial in pediatric patients with neuronopathic mucopolysaccharidosis II.Orphanet journal of rare diseases · 2024Trial
- Pharmacokinetic Modeling of Intrathecally Administered Recombinant Human Arylsulfatase A (TAK-611) in Children With Metachromatic Leukodystrophy.Clinical pharmacology and therapeutics · 2020Trial
- A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Trial
- Intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II: Results from a phase 2/3 randomized study.Molecular genetics and metabolismTrial
- Long-term open-label extension study of the safety and efficacy of intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II.Molecular genetics and metabolismTrial
- Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain.Fluids and barriers of the CNS · 2026Review
- rAAV9 vector biodistribution in nonhuman primate brain and spinal cord following lumbar intrathecal infusion.Frontiers in medicine · 2026Article
- Review
- Targeting Neurological Aspects of Mucopolysaccharidosis Type II: Enzyme Replacement Therapy and Beyond.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Evaluating the effect of injection protocols on intrathecal solute dispersion in non-human primates: an in vitro study using a cynomolgus cerebrospinal fluid system.Fluids and barriers of the CNS · 2024Article
- Effects of buoyancy on the dispersion of drugs released intrathecally in the spinal canal.Journal of fluid mechanics · 2024Article
- Clinical characteristics and somatic burden of patients with mucopolysaccharidosis II with or without neurological involvement: An analysis from the Hunter Outcome Survey.Molecular genetics and metabolism reports · 2023Article
- Neurodevelopmental status and adaptive behavior of pediatric patients with mucopolysaccharidosis II: a longitudinal observational study.Orphanet journal of rare diseases · 2023Observational
- 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
- Mucopolysaccharidoses and the blood-brain barrier.Fluids and barriers of the CNS · 2022Review
- Human in silico trials for parametric computational fluid dynamics investigation of cerebrospinal fluid drug delivery: impact of injection location, injection protocol, and physiology.Fluids and barriers of the CNS · 2022Article
- Investigation of Human Intrathecal Solute Transport Dynamics Using a NovelFrontiers in neuroimaging · 2022Article
- Analysis of cognitive ability and adaptive behavior assessment tools used in an observational study of patients with mucopolysaccharidosis II.Orphanet journal of rare diseases · 2021Observational
- Differences in MPS I and MPS II Disease Manifestations.International journal of molecular sciences · 2021Review
- Impact of intracerebroventricular enzyme replacement therapy in patients with neuronopathic mucopolysaccharidosis type II.Molecular therapy. Methods & clinical development · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals.
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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.