ArticleJCI insight2019
Hepatic arginase deficiency fosters dysmyelination during postnatal CNS development.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 19 citations in OpenAlex.
- Clinical Characteristics of Arginase 1 Deficiency: Natural History Insights From International Clinical Trials.Journal of inherited metabolic disease · 2026Article
- Astrocyte heterogeneity and gliosis in Huntington's disease: Histopathological insights into striatal and white matter pathology.Histology and histopathology · 2026Review
- Gene therapy for urea cycle defects: An update from historical perspectives to future prospects.Journal of inherited metabolic disease · 2024Review
- The role and control of arginine levels in arginase 1 deficiency.Journal of inherited metabolic disease · 2023Review
- Acetyl-11-keto-beta-boswellic acid promotes sciatic nerve repair after injury: molecular mechanism.Neural regeneration research · 2022Article
- Modelling urea cycle disorders using iPSCs.NPJ Regenerative medicine · 2022Review
- Intermittent lipid nanoparticle mRNA administration prevents cortical dysmyelination associated with arginase deficiency.Molecular therapy. Nucleic acids · 2022Article
- The effect of liver transplantation for argininemia-the largest experiences in a single center.Translational pediatrics · 2022Article
- Fifteen years of urea cycle disorders brain research: Looking back, looking forward.Analytical biochemistry · 2022Review
- Neurophysiological characteristics in argininemia: a case report.Translational pediatrics · 2021Article
- CPS1: Looking at an ancient enzyme in a modern light.Molecular genetics and metabolism · 2020Review
- Spinal Cord Involvement in Pediatric-Onset Metabolic Disorders With Mendelian and Mitochondrial Inheritance.Frontiers in pediatrics · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Deficiency of arginase is associated with hyperargininemia, and prominent features include spastic diplegia/tetraplegia, clonus, and hyperreflexia; loss of ambulation, intellectual disability and progressive neurological decline are other signs. To gain greater insight into the unique neuromotor features, we performed gene expression profiling of the motor cortex of a murine model of the disorder. Coexpression network analysis suggested an abnormality with myelination, which was supported by limited existing human data. Utilizing electron microscopy, marked dysmyelination was detected in 2-week-old homozygous Arg1-KO mice. The corticospinal tract was found to be adversely affected, supporting dysmyelination as the cause of the unique neuromotor features and implicating oligodendrocyte impairment in a deficiency of hepatic Arg1. Following neonatal hepatic gene therapy to express Arg1, the subcortical white matter, pyramidal tract, and corticospinal tract all showed a remarkable recovery in terms of myelinated axon density and ultrastructural integrity with active wrapping of axons by nearby oligodendrocyte processes. These findings support the following conclusions: arginase deficiency is a leukodystrophy affecting the brain and spinal cord while sparing the peripheral nervous system, and neonatal AAV hepatic gene therapy can rescue the defects associated with myelinated axons, strongly implicating the functional recovery of oligodendrocytes after restoration of hepatic arginase activity.
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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.