ArticleHuman molecular genetics2015
Human recombinant arginase enzyme reduces plasma arginine in mouse models of arginase deficiency.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00237315 (Longitudinal Study of Urea Cycle Disorders), which is not on this map. Cited by 27 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.
Longitudinal Study of Urea Cycle Disorders
Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency.Journal of inherited metabolic disease · 2021Trial
- Efficacy and safety of pegzilarginase in patients below 2 years of age with arginase 1 deficiency: a phase 3, open-label, multi-centre study.EClinicalMedicine · 2026Article
- Extracellular Vesicles Delivered a Functional ARG1 Enzyme and Restored Its Activity in a Mouse Model of ARG1-D Resulting in Improved Lifespan.International journal of molecular sciences · 2026Article
- Clinical Characteristics of Arginase 1 Deficiency: Natural History Insights From International Clinical Trials.Journal of inherited metabolic disease · 2026Article
- Arginase 1 deficiency: a treatable form of spastic paraplegia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Inherited metabolic epilepsies-established diseases, new approaches.Epilepsia open · 2024Review
- Plasma arginine levels in arginase deficiency in the "real world".Molecular genetics and metabolism reports · 2024Article
- Efficacy and safety of pegzilarginase in arginase 1 deficiency (PEACE): a phase 3, randomized, double-blind, placebo-controlled, multi-centre trial.EClinicalMedicine · 2024Article
- Human arginase I: a potential broad-spectrum anti-cancer agent.3 Biotech · 2023Review
- The role and control of arginine levels in arginase 1 deficiency.Journal of inherited metabolic disease · 2023Review
- Arginase 1 Deficiency in Patients Initially Diagnosed with Hereditary Spastic Paraplegia.Movement disorders clinical practice · 2023Review
- Human arginase 1, a Jack of all trades?3 Biotech · 2022Review
- Arginine depriving enzymes: applications as emerging therapeutics in cancer treatment.Cancer chemotherapy and pharmacology · 2021Review
- Primary hyperammonaemia: Current diagnostic and therapeutic strategies.Journal of mother and child · 2020Review
- Genome editing technologies to treat rare liver diseases.Translational gastroenterology and hepatology · 2020Review
- Messenger RNA therapy as an option for treating metabolic disorders.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Lipid nanoparticle-targeted mRNA therapy as a treatment for the inherited metabolic liver disorder arginase deficiency.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Untargeted metabolomic profiling reveals multiple pathway perturbations and new clinical biomarkers in urea cycle disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Polymer-drug conjugate therapeutics: advances, insights and prospects.Nature reviews. Drug discovery · 2019Review
- Transplantation of Gene-Edited Hepatocyte-like Cells Modestly Improves Survival of Arginase-1-Deficient Mice.Molecular therapy. Nucleic acids · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Arginase deficiency is caused by deficiency of arginase 1 (ARG1), a urea cycle enzyme that converts arginine to ornithine. Clinical features of arginase deficiency include elevated plasma arginine levels, spastic diplegia, intellectual disability, seizures and growth deficiency. Unlike other urea cycle disorders, recurrent hyperammonemia is typically less severe in this disorder. Normalization of plasma arginine levels is the consensus treatment goal, because elevations of arginine and its metabolites are suspected to contribute to the neurologic features. Using data from patients enrolled in a natural history study conducted by the Urea Cycle Disorders Consortium, we found that 97% of plasma arginine levels in subjects with arginase deficiency were above the normal range despite conventional treatment. Recently, arginine-degrading enzymes have been used to deplete arginine as a therapeutic strategy in cancer. We tested whether one of these enzymes, a pegylated human recombinant arginase 1 (AEB1102), reduces plasma arginine in murine models of arginase deficiency. In neonatal and adult mice with arginase deficiency, AEB1102 reduced the plasma arginine after single and repeated doses. However, survival did not improve likely, because this pegylated enzyme does not enter hepatocytes and does not improve hyperammonemia that accounts for lethality. Although murine models required dosing every 48 h, studies in cynomolgus monkeys indicate that less frequent dosing may be possible in patients. Given that elevated plasma arginine rather than hyperammonemia is the major treatment challenge, we propose that AEB1102 may have therapeutic potential as an arginine-reducing agent in patients with arginase deficiency.
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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.