ArticleJournal of the American Society of Nephrology : JASN2017
An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria.
Article in Journal of the American Society of Nephrology : JASN, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 199 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial.Pediatric nephrology (Berlin, Germany) · 2023Trial
- Animal Models of Hyperoxaluria and Their Relevance for Fundamental Research and Clinical Practice.International journal of molecular sciences · 2026Review
- 2'-Ribose-modified nucleotides: A strategy for reducing off-target effects of oligonucleotide drugs.Molecular therapy. Nucleic acids · 2026Article
- Targeting Oxalate Production by Combining Enzyme Inhibition and Proteolysis Activation: A Novel Therapeutic Approach for Primary Hyperoxaluria Type 1.Journal of medicinal chemistry · 2026Article
- Current status of primary hyperoxaluria type 1 in Japan.Urolithiasis · 2026Review
- Genetic and Clinical Characterization of a Large Cohort with Suspected Monogenic Stone Disease.Clinical journal of the American Society of Nephrology : CJASN · 2025Article
- How multispecific molecules are transforming pharmacotherapy.Nature reviews. Drug discovery · 2025Review
- Modified unlocked nucleic acid (MUNA) mitigates off-target effects of small interfering RNAs.Nucleic acids research · 2025Article
- Variable treatment response to lumasiran in pediatric patients with primary hyperoxaluria type 1.Pediatric nephrology (Berlin, Germany) · 2025Observational
- Preclinical evaluation of AGT mRNA replacement therapy for primary hyperoxaluria type I disease.Science advances · 2025Article
- Nucleic acid therapeutics: Past, present, and future.Molecular therapy. Nucleic acids · 2025Review
- Chemical engineering of CRISPR-Cas systems for therapeutic application.Nature reviews. Drug discovery · 2025Review
- Nucleic Acid Conjugates: Unlocking Therapeutic Potential.ACS bio & med chem Au · 2025Review
- Important Aspects of siRNA Design for Optimal Efficacy In Vitro and In Vivo.International journal of cell biology · 2025Review
- Lipid nanoparticle-mediated base-editing of the Hao1 gene achieves sustainable primary hyperoxaluria type 1 therapy in rats.Science China. Life sciences · 2024Article
- Amphiphilic Oligonucleotide Derivatives-Promising Tools for Therapeutics.Pharmaceutics · 2024Review
- Mutation Characteristics of Primary Hyperoxaluria in the Chinese Population and Current International Diagnosis and Treatment Status.Kidney diseases (Basel, Switzerland) · 2024Review
- Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial.Kidney international reports · 2024Article
- Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs.Biomolecules · 2024Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Primary hyperoxaluria type 1 (PH1), an inherited rare disease of glyoxylate metabolism, arises from mutations in the enzyme alanine-glyoxylate aminotransferase. The resulting deficiency in this enzyme leads to abnormally high oxalate production resulting in calcium oxalate crystal formation and deposition in the kidney and many other tissues, with systemic oxalosis and ESRD being a common outcome. Although a small subset of patients manages the disease with vitamin B6 treatments, the only effective treatment for most is a combined liver-kidney transplant, which requires life-long immune suppression and carries significant mortality risk. In this report, we discuss the development of ALN-GO1, an investigational RNA interference (RNAi) therapeutic targeting glycolate oxidase, to deplete the substrate for oxalate synthesis. Subcutaneous administration of ALN-GO1 resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and increased serum glycolate concentrations in wild-type mice, rats, and nonhuman primates. ALN-GO1 also increased urinary glycolate concentrations in normal nonhuman primates and in a genetic mouse model of PH1. Notably, ALN-GO1 reduced urinary oxalate concentration up to 50% after a single dose in the genetic mouse model of PH1, and up to 98% after multiple doses in a rat model of hyperoxaluria. These data demonstrate the ability of ALN-GO1 to reduce oxalate production in preclinical models of PH1 across multiple species and provide a clear rationale for clinical trials with this compound.
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.