DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for focal segmental glomerulosclerosis 1 — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFocal segmental glomerulosclerosis 1 maps to a 3-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 1 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.
Molecular view
actinin alpha 4 (ACTN4) — ACTN4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6OA6 · 1.37 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Focal segmental glomerulosclerosis is a histologic pattern defined by sclerosis in some segments of certain glomeruli, with podocyte foot process effacement seen on electron microscopy. Podocytes are highly differentiated cells with limited regenerative capacity, and their reduction in number drives the injury. The heterogeneity in underlying causes of podocyte loss produces equally variable clinical phenotypes. Recent work has redefined the classification of FSGS by acknowledging advances in defining its genetic and immunologic basis.
Unprecedented clinical trial activity and efficacy of repurposed agents have been reported, but the 2022 minireview does not name specific drugs or give concrete numbers for survival or response rates. A 2019 review states that multiple treatment options such as steroids have been tried, but most showed only partial response, increased relapses after completing treatment, and increased adverse effects due to prolonged use. If left untreated, FSGS progressively damages enough glomeruli to cause a fall in glomerular filtration rate, producing renal failure and requiring renal replacement therapy.
A 2015 article discusses advances in understanding the genetics behind FSGS, noting that many advances have been made but more research is needed to identify additional susceptibility genes and, more importantly, to understand the underlying pathophysiology. The article discusses familial FSGS presented during the first Michelle Winn Endowed Lecture at Kidney Week 2014, but provides no specific mutation frequencies or trial outcomes.
What is still missing are large, randomised controlled trials with hard renal endpoints, validated biomarkers to stratify patients by genetic or immunologic subtype, and funding to move beyond small case series and reviews that describe hope without providing reproducible efficacy data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Kidney International Reports · 2022 · 31 citations · open access
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.
Family Medicine and Primary Care Open Access · 2019 · 0 citations · open access
Focal Segmental Glomerulosclerosis and the Role of ACTH
AbstractFocal Segmental Glomerulosclerosis (FSGS) is one of the common causes of nephrotic syndromes, manifested by heavy proteinuria, minimal hematuria and hypoalbuminemia. If left undiagnosed or untreated, FSGS will progressively damage enough glomeruli to cause a fall in Glomerular Filtration Rate (GFR) producing renal failure and require renal replacement therapy. For this reason, early identification and treatment is warranted to delay disease progression. Multiple treatment options such as steroids have been tried but most of these treatments showed partial response, increased relapses after completing treatment course and increased adverse effects due to prolonged use.
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.
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.
