ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Specific Inhibition of Hepatic Lactate Dehydrogenase Reduces Oxalate Production in Mouse Models of Primary Hyperoxaluria.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 104 citations in OpenAlex.
- Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8).Pediatric nephrology (Berlin, Germany) · 2025Trial
- Lactylation enzymes in cancer: Mechanisms and novel therapeutic approaches (Review).Oncology letters · 2026Review
- Targeting Oxalate Production by Combining Enzyme Inhibition and Proteolysis Activation: A Novel Therapeutic Approach for Primary Hyperoxaluria Type 1.Journal of medicinal chemistry · 2026Article
- How multispecific molecules are transforming pharmacotherapy.Nature reviews. Drug discovery · 2025Review
- Population Pharmacokinetic and Pharmacodynamic Modelling and Simulation for Nedosiran Clinical Development and Dose Guidance in Pediatric Patients with Primary Hyperoxaluria Type 1.Clinical pharmacokinetics · 2025Article
- Preclinical evaluation of AGT mRNA replacement therapy for primary hyperoxaluria type I disease.Science advances · 2025Article
- 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
- Moderate aerobic exercise improves haematological indices without altering cardio-metabolic enzyme activities in sedentary healthy young adults.BMC sports science, medicine & rehabilitation · 2025Article
- Lipid nanoparticle-mediated base-editing of the Hao1 gene achieves sustainable primary hyperoxaluria type 1 therapy in rats.Science China. Life sciences · 2024Article
- 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
- Article
- Synthesis of Ethyl Pyrimidine-Quinolincarboxylates Selected from Virtual Screening as Enhanced Lactate Dehydrogenase (LDH) Inhibitors.International journal of molecular sciences · 2024Article
- The 60-year evolution of lipid nanoparticles for nucleic acid delivery.Nature reviews. Drug discovery · 2024Review
- 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
- Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs.Biomolecules · 2024Review
- Nucleic Acid Therapeutics: Successes, Milestones, and Upcoming Innovation.Nucleic acid therapeutics · 2024Review
- 2023 FDA TIDES (Peptides and Oligonucleotides) Harvest.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Multicenter Long-Term Real World Data on Treatment With Lumasiran in Patients With Primary Hyperoxaluria Type 1.Kidney international reports · 2024Article
- Nedosiran: First Approval.Drugs · 2023Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary hyperoxalurias (PHs) are autosomal recessive disorders caused by the overproduction of oxalate leading to calcium oxalate precipitation in the kidney and eventually to end-stage renal disease. One promising strategy to treat PHs is to reduce the hepatic production of oxalate through substrate reduction therapy by inhibiting liver-specific glycolate oxidase (GO), which controls the conversion of glycolate to glyoxylate, the proposed main precursor to oxalate. Alternatively, diminishing the amount of hepatic lactate dehydrogenase (LDH) expression, the proposed key enzyme responsible for converting glyoxylate to oxalate, should directly prevent the accumulation of oxalate in PH patients. Using RNAi, we provide the first in vivo evidence in mammals to support LDH as the key enzyme responsible for converting glyoxylate to oxalate. In addition, we demonstrate that reduction of hepatic LDH achieves efficient oxalate reduction and prevents calcium oxalate crystal deposition in genetically engineered mouse models of PH types 1 (PH1) and 2 (PH2), as well as in chemically induced PH mouse models. Repression of hepatic LDH in mice did not cause any acute elevation of circulating liver enzymes, lactate acidosis, or exertional myopathy, suggesting further evaluation of liver-specific inhibition of LDH as a potential approach for treating PH1 and PH2 is warranted.
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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.