ArticleThe Journal of clinical investigation2007
Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06664814 (An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine), which is not on this map. Cited by 119 papers.
What it found
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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.
An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Podocyte Diseases
Who cites it
119 citing papers in PubMed, 199 citations in OpenAlex.
- Alternative Dosing Strategies to Enhance the Absorption of N-Acetyl-D-Mannosamine Monohydrate (ManNAc) in Healthy Adult Males.Clinical drug investigation · 2026Trial
- Impact of Food on the Oral Absorption of N-Acetyl-D-Mannosamine in Healthy Men and Women.Clinical pharmacology in drug development · 2024Trial
- Safety, pharmacokinetics and sialic acid production after oral administration of N-acetylmannosamine (ManNAc) to subjects with GNE myopathy.Molecular genetics and metabolism · 2017Trial
- Aceneuramic Acid Extended Release Administration Maintains Upper Limb Muscle Strength in a 48-week Study of Subjects with GNE Myopathy: Results from a Phase 2, Randomized, Controlled Study.Journal of neuromuscular diseases · 2016Trial
- Preclinical assessment of GNEFuture science OA · 2026Article
- GNE Myopathy: 25 Years After Gene Identification-Facts, Controversies, Enigmas, Prospects.Journal of clinical medicine · 2026Review
- Modulating the sialic acid content of endothelial cells affects their adhesion and barrier permeability.Scientific reports · 2026Article
- IgM Hyposialylation Modulates Podocyte Vulnerability in Patients With Idiopathic Nephrotic Syndrome.Kidney international reports · 2026Article
- Biosynthetic and genetic pathways related to sialic acid metabolism.The Journal of biological chemistry · 2026Review
- Article
- Defective autophagy in GNE myopathy is rescued by inhibition of noncanonical Akt-mTORC1 activation across multiple isogenic models.Experimental & molecular medicine · 2026Article
- Phase 1 Study of Oral N-Acetylmannosamine in Primary Podocytopathies.Kidney international reports · 2026Article
- Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease.Nature communications · 2024Article
- Normal and Dysregulated Sphingolipid Metabolism: Contributions to Podocyte Injury and Beyond.Cells · 2024Review
- Novel GNE missense variants impair de novo sialylation and cause defective angiogenesis in the developing brain in mice.Blood advances · 2024Article
- Understanding pathophysiology of GNE myopathy and current progress towards drug development.Journal of biosciences · 2024Review
- Induced Muscle and Liver Absence of Gne in Postnatal Mice Does Not Result in Structural or Functional Muscle Impairment.Journal of neuromuscular diseases · 2024Article
- Severe kidney dysfunction in sialidosis mice reveals an essential role for neuraminidase 1 in reabsorption.JCI insight · 2023Article
- Article
- Glycation Interferes with the Activity of the Bi-Functional UDP-Biomolecules · 2023Article
59 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the key enzyme of sialic acid biosynthesis, uridine diphospho-N-acetylglucosamine 2-epimerase/N-acetylmannosamine (ManNAc) kinase (GNE/MNK), result in hereditary inclusion body myopathy (HIBM), an adult-onset, progressive neuromuscular disorder. We created knockin mice harboring the M712T Gne/Mnk mutation. Homozygous mutant (Gne(M712T/M712T)) mice did not survive beyond P3. At P2, significantly decreased Gne-epimerase activity was observed in Gne(M712T/M712T) muscle, but no myopathic features were apparent. Rather, homozygous mutant mice had glomerular hematuria, proteinuria, and podocytopathy. Renal findings included segmental splitting of the glomerular basement membrane, effacement of podocyte foot processes, and reduced sialylation of the major podocyte sialoprotein, podocalyxin. ManNAc administration yielded survival beyond P3 in 43% of the Gne(M712T/M712T) pups. Survivors exhibited improved renal histology, increased sialylation of podocalyxin, and increased Gne/Mnk protein expression and Gne-epimerase activities. These findings establish this Gne(M712T/M712T) knockin mouse as what we believe to be the first genetic model of podocyte injury and segmental glomerular basement membrane splitting due to hyposialylation. The results also support evaluation of ManNAc as a treatment not only for HIBM but also for renal disorders involving proteinuria and hematuria due to podocytopathy and/or segmental splitting of the glomerular basement membrane.
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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.