ArticleBiochimica et biophysica acta. Molecular basis of disease2019
Reduction in urinary oxalate excretion in mouse models of Primary Hyperoxaluria by RNA interference inhibition of liver lactate dehydrogenase activity.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 41 citations in OpenAlex.
- Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8).Pediatric nephrology (Berlin, Germany) · 2025Trial
- Characterization of CHK-336, A First-in-Class, Liver-Targeted, Small-Molecule Lactate Dehydrogenase Inhibitor for Hyperoxaluria Treatment.Journal of the American Society of Nephrology : JASN · 2025Article
- Lactate and Lactylation: Dual Regulators of T-Cell-Mediated Tumor Immunity and Immunotherapy.Biomolecules · 2024Review
- Nedosiran population pharmacokinetic and pharmacodynamic modelling and simulation to guide clinical development and dose selection in patients with primary hyperoxaluria type 1.British journal of clinical pharmacology · 2024Article
- Mutation Characteristics of Primary Hyperoxaluria in the Chinese Population and Current International Diagnosis and Treatment Status.Kidney diseases (Basel, Switzerland) · 2024Review
- Nedosiran Safety and Efficacy in PH1: Interim Analysis of PHYOX3.Kidney international reports · 2024Article
- Non-Coding RNAs in Kidney Stones.Biomolecules · 2024Review
- Multiplex gene editing reduces oxalate production in primary hyperoxaluria type 1.Zoological research · 2023Article
- Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4).Urolithiasis · 2023Article
- SLC26 family: a new insight for kidney stone disease.Frontiers in physiology · 2023Review
- Mitochondrial might: powering the peripartum for risk and resilience.Frontiers in behavioral neuroscience · 2023Review
- Natural compounds as lactate dehydrogenase inhibitors: potential therapeutics for lactate dehydrogenase inhibitors-related diseases.Frontiers in pharmacology · 2023Review
- Oxalate as a potent promoter of kidney stone formation.Frontiers in medicine · 2023Review
- Nedosiran, a Candidate siRNA Drug for the Treatment of Primary Hyperoxaluria: Design, Development, and Clinical Studies.ACS pharmacology & translational science · 2022Review
- Therapeutic RNA interference: A novel approach to the treatment of primary hyperoxaluria.British journal of clinical pharmacology · 2022Review
- Clinical Applications of Short Non-Coding RNA-Based Therapies in the Era of Precision Medicine.Cancers · 2022Review
- Lumasiran for primary hyperoxaluria type 1: What we have learned?Frontiers in pediatrics · 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
- Recovery From Dialysis in Patients With Primary Hyperoxaluria Type 1 Treated With Pyridoxine: A Report of 3 Cases.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2021Article
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6 authors at 2 institutions in 1 country.
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Abstract
The Primary Hyperoxaluria's (PH) are rare autosomal recessive disorders characterized by elevated oxalate production. PH patients suffer recurrent calcium oxalate kidney stone disease, and in severe cases end stage renal disease. Recent evidence has shown that RNA interference may be a suitable approach to reduce oxalate production in PH patients by knocking down key enzymes involved in hepatic oxalate synthesis. In the current study, wild type mice and mouse models of PH1 (AGT KO) and PH2 (GR KO) were treated with siRNA that targets hepatic LDHA. Although siRNA treatment substantially reduced urinary oxalate excretion [75%] in AGT KO animals, there was a relatively modest reduction [32%] in GR KO animals. Plasma and liver pyruvate levels significantly increased with siRNA treatment and liver organic acid analysis indicated significant changes in a number of glycolytic and TCA cycle metabolites, consistent with the known role of LDHA in metabolism. However, siRNA dosing data suggest that it may be possible to identify a dose that limits changes in liver organic acid levels, while maintaining a desired effect of reducing glyoxylate to oxalate synthesis. These results suggest that RNAi mediated reduction of hepatic LDHA may be an effective strategy to reduce oxalate synthesis in PH, and further analysis of its metabolic effects should be explored. Additional studies should also clarify in GR KO animals whether there are alternate enzymatic pathways in the liver to create oxalate and whether tissues other than liver contribute significantly to oxalate production.
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