ArticleAmerican journal of human genetics2012
Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Nitric Oxide Supplementation as a Therapeutic Intervention in Argininosuccinic Aciduria
Effect of Nitric Oxide (NO) Supplementation on Neurocognitive Measures in Argininosuccinate Lyase Deficiency (ASLD)
Who cites it
30 citing papers in PubMed, 82 citations in OpenAlex.
- Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation.The Journal of clinical investigation · 2021Trial
- Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension.American journal of human genetics · 2018Trial
- Acute effects of an oral nitric oxide supplement on blood pressure, endothelial function, and vascular compliance in hypertensive patients.Journal of clinical hypertension (Greenwich, Conn.) · 2014Trial
- A randomized controlled trial to evaluate the effects of high-dose versus low-dose of arginine therapy on hepatic function tests in argininosuccinic aciduria.Molecular genetics and metabolism · 2012Trial
- Revisiting gut microbiota-driven ammonia metabolism: from disease burden to physiological adaptation.Gut microbes · 2026Review
- Article
- Current Treatment Modalities for Urea Cycle Disorders.Paediatric drugs · 2025Review
- Clinical, biochemical and genetic characteristics of patients with argininosuccinate lyase deficiency from a single center cohort in China.Orphanet journal of rare diseases · 2025Article
- Enhanced functional properties and volatile profiles in Lactobacillus-fermentedFood chemistry: X · 2025Article
- Inherited metabolic epilepsies-established diseases, new approaches.Epilepsia open · 2024Review
- The incidence of movement disorder increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria.Journal of inherited metabolic disease · 2024Article
- mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria.Science translational medicine · 2024Article
- Gene therapy for urea cycle defects: An update from historical perspectives to future prospects.Journal of inherited metabolic disease · 2024Review
- Argininosuccinate lyase deficiency causes blood-brain barrier disruption via nitric oxide-mediated dysregulation of claudin expression.JCI insight · 2023Article
- Modelling urea cycle disorders using iPSCs.NPJ Regenerative medicine · 2022Review
- ASL expression in ALDH1A1Human genetics · 2021Article
- Beclin-1-mediated activation of autophagy improves proximal and distal urea cycle disorders.EMBO molecular medicine · 2021Article
- Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy.Nature reviews. Nephrology · 2020Review
- Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency.JCI insight · 2020Article
- Update on Gaseous Signaling Molecules Nitric Oxide and Hydrogen Sulfide: Strategies to Capture their Functional Activity for Human Therapeutics.Molecular pharmacology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea-cycle disorder, and leads to deficiency of both ureagenesis and NO production. Subjects with ASA have been reported to develop long-term complications such as hypertension and neurocognitive deficits despite early initiation of therapy and the absence of documented hyperammonemia. In order to distinguish the relative contributions of the hepatic urea-cycle defect from those of the NO deficiency to the phenotype, we performed liver-directed gene therapy in a mouse model of ASA. Whereas the gene therapy corrected the ureagenesis defect, the systemic hypertension in mice could be corrected by treatment with an exogenous NO source. In an ASA subject with severe hypertension refractory to antihypertensive medications, monotherapy with NO supplements resulted in the long-term control of hypertension and a decrease in cardiac hypertrophy. In addition, the NO therapy was associated with an improvement in some neuropsychological parameters pertaining to verbal memory and nonverbal problem solving. Our data show that ASA, in addition to being a classical urea-cycle disorder, is also a model of congenital human NO deficiency and that ASA subjects could potentially benefit from NO supplementation. Hence, NO supplementation should be investigated for the long-term treatment of this condition.
Indexed as
Identifiers
What OpenQuestion holds
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.