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Nephrology Lab · DeCure for X

DeCure for Focal segmental glomerulosclerosis 9

DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for focal segmental glomerulosclerosis 9 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.

Disease module1 genesLead labNephrology
All cures
NephrologyDOID:0111134$DeCureNephro

The disease map

Disease moduleFocal segmental glomerulosclerosis 9 maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.

Research record

01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash

Current lead

No approved-drug candidate for focal segmental glomerulosclerosis 9 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.

What the evidence adds up to

In focal segmental glomerulosclerosis (FSGS), a histologic pattern defined by segmental sclerosis in some glomeruli, podocyte loss is central. The condition is heterogeneous in cause and clinical phenotype. A 2022 minireview notes that recent work on genetic and immunologic disease classification, along with clinical trial activity for repurposed agents, has created hope for improved options, but the review does not report any specific efficacy data from those trials.

A 2021 bioinformatics study analysed three microarray datasets from kidney tissue of FSGS patients and healthy controls. It identified 85 differentially expressed genes common to all three datasets, of which 16 were up-regulated and 69 down-regulated. Four hub genes with the highest degree of interaction were fibronectin-1 (FN1), complement C3, collagen type IV alpha 1 (COL4A1), and integrin beta-6 (ITGB6). Pathway analysis pointed to extracellular matrix organisation, ECM proteoglycans, and integrin-mediated signalling. The study is purely computational; it does not test any drug or treatment.

A 2020 protocol for a systematic review and meta-analysis of randomised controlled trials of calcineurin inhibitors in primary FSGS states that FSGS is a leading cause of kidney disease worldwide, with annual incidence rates of 0.2 to 1.8 per 100,000 population. The protocol describes the planned analysis but provides no results. A 2015 article on genetic mutations in FSGS similarly reports no treatment data.

No abstract in this set provides evidence that any drug, repurposed or otherwise, improves clinical outcomes in FSGS. The bioinformatics study identifies potential molecular targets, but these have not been validated in patients. What is missing are adequately powered randomised trials that test specific repurposed agents in well-stratified FSGS populations, along with funding to move from gene lists to clinical testing.

Evidence

Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.

Annual Review of Medicine · 1984 · 50 citations

Focal Segmental Glomerulosclerosis

AbstractFocal segmental glomerulosclerosis is an important cause of the nephrotic syndrome in children and adults. This paper reviews the pathogenesis, clinical manifestations, morphology, and treatment of focal glomerulosclerosis. In addition, it considers the recently described association of focal glomerulosclerosis with nonglomerular renal diseases and the possible role of this glomerular lesion in progressive renal failure.

https://doi.org/10.1146/annurev.me.35.020184.002241
Kidney International Reports · 2022 · 31 citations · open access

Novel Treatment Paradigms: Focal Segmental Glomerulosclerosis

AbstractFocal segmental glomerulosclerosis (FSGS) is a histologic pattern of injury defined by the presence of sclerosis in some (segmental) of certain glomeruli (focal). On electron microscopy, it is characterized by a variable degree of podocyte foot process effacement and gaps in the coverage of the glomerular basement membrane. The pattern of injury occurs when podocytes, highly differentiated cells with limited regenerative capacity, are reduced in number. The heterogeneity in underlying causes of podocyte loss results in equally variable clinical phenotypes. Recent work acknowledging advances in defining the genetic and immunologic basis of disease has redefined the classification of FSGS. Unprecedented clinical trial activity and efficacy of repurposed agents presents hope for improved therapeutic options. This minireview summarizes recent advances with a focus on novel treatment paradigms in FSGS.

https://doi.org/10.1016/j.ekir.2022.10.004
International Journal of Applied Biology and Pharmaceutical Technology · 2021 · 4 citations · open access

Identification of Crucial Degs and Hub Genes in Focal Segmental Glomerulosclerosis: A Bioinformatics Study

AbstractAims In individuals with focal segmental glomerulosclerosis, identify the important differentially expressed genes (DEGs) relative to healthy control, in kidney tissue samples (glomeruli and tubulointerstitium tissue) and examine their probable role in the molecular mechanism and pathogenesis process of disease. Methods From the Gene Expression Omnibus (GEO) database, raw microarray data generated from kidney tissues from focal segmental glomerulosclerosis patients, and healthy controls patients (GSE121233, GSE125779, GSE129973) were retrieved. Transcription analysis console 4.0 was used to identify DEGs. FUNRICH (Functional enrichment analysis tools) and Enrichr were used to perform functional gene enrichment analysis. Then, Search Tool for Retrieval Interacting Genes (STRING) 10.0 for PPI analysis and cyto scape's for network visualization was used. Further hub genes were identified using the cytohubbaalogorithm plug-in. Then KEGG and REACTOME databases were integrated with Shiny Go and FUNRICH to perform pathway analysis. We used GSEA analysis and associated pathway enrichment by metascape analysis utilizing the molecular complex identification (MCODE) algorithm to discover densely linked network components to further elucidate the likely mechanism of action of related genes in FSGS. The MCODE networks identified for individual gene lists have been gathered. Pathway and process enrichment analysis has been applied to each MCODE component independently, and the three best-scoring terms by p-value have been retained as the functional description of the corresponding components, shown in the tables underneath corresponding network plots further cross validation was done by ORA (over representation analysis) for the commonly (up-regulated) genes including hubgene from all three datasets was done by webgestalt. Finally, we check the raw expression level of all up regulated DEGs, including hub genes, in one main data set (GSE121233) and one validation dataset (GSE129973) to validate the expression of genes identified. We also checked the gene expression level in ERCB (RNA-seq) datasets for various kidney diseases with diabetes including FSGS and other demographic parameters such as GFR and proteinuria, as well as gene expression in gender by using nephroseq. Results 85 DEGs were co-expressed in the three datasets, out of which 16 genes were up-regulated and 69 genes were down regulated in FSGS. DEGs are mostly involved in extracellular matrix organization (biological process), extracellular matrix proteoglycans and integrins cell surface interaction (biological pathways). Protein–protein interaction (PPI) network of 16 upregulated degs in FSGS, identified 43 co expressed genes out of which 20 genes as hub gene where identified by cytohubba, four high ranked hubgenes with greater degree of interaction were (Fibronectin-1, Complement C3 & collagen, type IV, alpha 1, Integrin β6). Metascape analysis results suggests extracellular matrix organization and the genes involved to regulated this biological process are (COL4A1, FN1, ITGB6, LUM, ADAMTS1) shows highest interactions with ECM proteoglycans regulated by genes (COL4A1, FN1, ITGB6, LUM) and integrin mediated signaling pathways regulated by genes (COL4A1, FN1, ITGB6, LUM, ADAMTS1) with enrichment score 134 and 120 with p value p<0.01 and z score 21 and 14. Over representation analysis suggests FN1, C3, ITGB6, COL4A1, C7 and LUMgene is enriched in above stated pathways identified with enrichment ratio more than 50% with p value P<0.0001, GSEA suggests higher expression of genes in these pathways. Three datasets showed the same expression in average as well as raw signals, of upregulated genes including hub gene (LUM,ABCG1, ADAMTS1, C3, MIR4521, PIGR, FN1, COL4A1, MYOF, ITGB6, CLDN1, REN, CDH6, C7, HAVCR1, NR1D1) further each identified genes are checked in nephroseq database at RNA-seq levels for different demographics and other diabetes associated diseases, shown by box plot and bar graph as in our bioinformatics analysis. Conclusion In FSGS, bioinformatics analysis revealed 16 upregulated genes, including 11 crucial genes (HAVCR1, COL4A1, ABCG1, C3, ITGB6, LUM, MYOF, PIGR, C7, FN1, ADAMTS1) and 4 hub-genes (FN1, C3, ITGB6, COL4A1) with high rank and high degree of interaction from three FSGS datasets included in the study, indicating their involvement in FSGS pathways and suggesting they could be potential targets in the disease molecular mechanism.

https://doi.org/10.26502/ijabpt.202112
Open Science Framework · 2020 · 0 citations · open access

Calcineurin inhibitors in the treatment of primary focal segmental glomerulosclerosis: a protocol of systematic review and meta-analysis of randomized controlled trials

AbstractFocal segmental glomerulosclerosis (FSGS) is a leading cause of kidney diseases worldwide. The prevalence of FSGS, relative to other glomerular disease diagnoses, seems to be increasing worldwide, and it is a major contributor to end-stage renal disease (ESRD). In 2011, McGrogan et al. reported an annual incidence rates of FSGS as 0.2 to 1.8/100, 000 population per year by reviewing literature worldwide.

https://doi.org/10.17605/osf.io/3b7de
MD Conference Express · 2015 · 0 citations

Genetic Mutations Play a Role in FSGS

AbstractMany advances have been made in understanding the genetics behind focal segmental glomerulosclerosis (FSGS). However, more research is needed to identify additional susceptibility genes and, more importantly, to understand the underlying pathophysiology of FSGS. This article discusses familial FSGS that was presented during the first Michelle Winn Endowed Lecture at Kidney Week 2014.

https://doi.org/10.1177/155989771449011

Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.

DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.