ArticlePloS one2019
A systems pharmacology workflow with experimental validation to assess the potential of anakinra for treatment of focal and segmental glomerulosclerosis.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Integrative Analysis of Drug Co-Prescriptions in Peritoneal Dialysis Reveals Molecular Targets and Novel Strategies for Intervention.Journal of clinical medicine · 2025Article
- Clopidogrel for Proteinuria Reduction in Focal Segmental Glomerulosclerosis: Phase 2 Trial Design.Kidney international reports · 2024Article
- Repurposing drugs for diseases associated with podocyte dysfunction.Kidney international · 2023Review
- Deconvolution of Focal Segmental Glomerulosclerosis Pathophysiology Using Transcriptomics Techniques.Glomerular diseases · 2021Review
- Exploring the Molecular Mechanism of Action of Yinchen Wuling Powder for the Treatment of Hyperlipidemia, Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.BioMed research international · 2021Article
- Loss of decay-accelerating factor triggers podocyte injury and glomerulosclerosis.The Journal of experimental medicine · 2020Article
- BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis.Science translational medicine · 2020Article
- Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment.BMC complementary medicine and therapies · 2020Article
- Network Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Qiaoshao Formula for Treatment of Premature Ejaculation.Evidence-based complementary and alternative medicine : eCAM · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Focal and Segmental Glomerulosclerosis (FSGS) is a severe glomerulopathy that frequently leads to end stage renal disease. Only a subset of patients responds to current therapies, making it important to identify alternative therapeutic options. The interleukin (IL)-1 receptor antagonist anakinra is beneficial in several diseases with renal involvement. Here, we evaluated the potential of anakinra for FSGS treatment. Molecular process models obtained from scientific literature data were used to build FSGS pathology and anakinra mechanism of action models by exploiting information on protein interactions. These molecular models were compared by statistical interference analysis and expert based molecular signature matching. Experimental validation was performed in Adriamycin- and lipopolysaccharide (LPS)-induced nephropathy mouse models. Interference analysis (containing 225 protein coding genes and 8 molecular process segments) of the FSGS molecular pathophysiology model with the drug mechanism of action of anakinra identified a statistically significant overlap with 43 shared molecular features that were enriched in pathways relevant in FSGS, such as plasminogen activating cascade, inflammation and apoptosis. Expert adjudication of molecular signature matching, focusing on molecular process segments did not suggest a high therapeutic potential of anakinra in FSGS. In line with this, experimental validation did not result in altered proteinuria or significant changes in expression of the FSGS-relevant genes COL1A1 and NPHS1. In summary, an integrated bioinformatic and experimental workflow showed that FSGS relevant molecular processes can be significantly affected by anakinra beyond the direct drug target IL-1 receptor type 1 (IL1R1) context but might not counteract central pathophysiology processes in FSGS. Anakinra is therefore not suggested for extended preclinical trials.
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