ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Inhibition of Glycolate Oxidase With Dicer-substrate siRNA Reduces Calcium Oxalate Deposition in a Mouse Model of Primary Hyperoxaluria Type 1.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02795325 (A Phase 1 Study of DCR-PH1 in Patients With Primary Hyperoxaluria Type 1), which is not on this map. Cited by 47 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.
A Phase 1 Study of DCR-PH1 in Patients With Primary Hyperoxaluria Type 1 (PH1)
Who cites it
47 citing papers in PubMed, 82 citations in OpenAlex.
- Integrated transcriptomics, proteomics, and metabolomics to uncover inflammatory-metabolic crosstalk and key molecules in a mouse model of hyperoxaluria-induced kidney injury.Translational andrology and urology · 2025Article
- Review
- Advancing Therapeutic Strategies with Polymeric Drug Conjugates for Nucleic Acid Delivery and Treatment.International journal of nanomedicine · 2025Review
- Multicenter Long-Term Real World Data on Treatment With Lumasiran in Patients With Primary Hyperoxaluria Type 1.Kidney international reports · 2024Article
- Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1.EMBO molecular medicine · 2024Article
- Acetate attenuates hyperoxaluria-induced kidney injury by inhibiting macrophage infiltration via the miR-493-3p/MIF axis.Communications biology · 2023Article
- Lipid-based nucleic acid therapeutics with in vivo efficacy.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023Review
- Therapeutic siRNA: State-of-the-Art and Future Perspectives.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- HAO1-mediated oxalate metabolism promotes lung pre-metastatic niche formation by inducing neutrophil extracellular traps.Oncogene · 2022Article
- Review
- Article
- Therapeutic RNA interference: A novel approach to the treatment of primary hyperoxaluria.British journal of clinical pharmacology · 2022Review
- Therapeutic RNA-silencing oligonucleotides in metabolic diseases.Nature reviews. Drug discovery · 2022Review
- Hao1 Is Not a Pathogenic Factor for Ectopic Ossifications but Functions to Regulate the TCA Cycle In Vivo.Metabolites · 2022Article
- Lumasiran in the Management of Patients with Primary Hyperoxaluria Type 1: From Bench to Bedside.International journal of nephrology and renovascular disease · 2022Review
- Novel Starting Points for Human Glycolate Oxidase Inhibitors, Revealed by Crystallography-Based Fragment Screening.Frontiers in chemistry · 2022Article
- The therapeutic prospects of N-acetylgalactosamine-siRNA conjugates.Frontiers in pharmacology · 2022Review
- Back to the Future: The Role of Metabolic Studies in Therapeutic Advances.Journal of the American Society of Nephrology : JASN · 2021Article
- Novel therapeutic approaches for the primary hyperoxalurias.Pediatric nephrology (Berlin, Germany) · 2021Review
- Dual Glycolate Oxidase/Lactate Dehydrogenase A Inhibitors for Primary Hyperoxaluria.ACS medicinal chemistry letters · 2021Article
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Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary hyperoxaluria type 1 (PH1) is an autosomal recessive, metabolic disorder caused by mutations of alanine-glyoxylate aminotransferase (AGT), a key hepatic enzyme in the detoxification of glyoxylate arising from multiple normal metabolic pathways to glycine. Accumulation of glyoxylate, a precursor of oxalate, leads to the overproduction of oxalate in the liver, which accumulates to high levels in kidneys and urine. Crystalization of calcium oxalate (CaOx) in the kidney ultimately results in renal failure. Currently, the only treatment effective in reduction of oxalate production in patients who do not respond to high-dose vitamin B6 therapy is a combined liver/kidney transplant. We explored an alternative approach to prevent glyoxylate production using Dicer-substrate small interfering RNAs (DsiRNAs) targeting hydroxyacid oxidase 1 (HAO1) mRNA which encodes glycolate oxidase (GO), to reduce the hepatic conversion of glycolate to glyoxylate. This approach efficiently reduces GO mRNA and protein in the livers of mice and nonhuman primates. Reduction of hepatic GO leads to normalization of urine oxalate levels and reduces CaOx deposition in a preclinical mouse model of PH1. Our results support the use of DsiRNA to reduce liver GO levels as a potential therapeutic approach to treat PH1.
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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.