DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for focal segmental glomerulosclerosis — screening already-approved drugs against its 36-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 maps to a 36-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 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
collagen type IV alpha 5 chain (COL4A5) — COL4A5 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6WKU · 1.76 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
Focal segmental glomerulosclerosis accounts for 10–20% of patients of all ages who progress to end stage kidney disease, and there are no FDA approved therapeutic options that effectively prevent or delay the onset of kidney failure. Current immunosuppressive therapy and conservative management include inhibitors of the renin-angiotensin-aldosterone axis and sodium-glucose cotransporter inhibitors, but these are not curative. A 2019 review notes 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.
A 2021 phase II clinical trial, the FSGS Clinical Trial, was a multi-centre, prospective, controlled, open label randomised trial designed to determine whether treatment with mycophenolate mofetil in conjunction with pulse steroids is superior to treatment with cyclosporine-A in inducing remission from proteinuria over 12 months. The trial protocol is described, but no efficacy results are reported in the abstract. The same abstract states that evidence-based treatment guidelines have not been developed because of the lack of controlled studies and the small number of participants included in most reports.
A 2020 review of emerging drugs highlights that FSGS is now recognised as a heterogeneous entity with multiple underlying disease mechanisms. Novel approaches targeting the podocyte cytoskeleton, immunological, inflammatory, haemodynamic and metabolic pathways are being developed, but none are approved. The review also notes that growing awareness of the burden of chronic kidney disease, improved scientific understanding of injury mechanisms, and development of noninvasive profiles to identify subgroups of patients are driving drug development.
What is still missing are adequately powered, controlled trials with sufficient participant numbers to generate evidence-based treatment guidelines. The heterogeneity of FSGS means that patient stratification by discrete mechanisms of glomerular injury is needed, but validated noninvasive profiles to achieve this are not yet established. No drug mentioned in these abstracts has demonstrated definitive efficacy in a completed randomised controlled trial.
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.
Expert Opinion on Emerging Drugs · 2020 · 26 citations · open access
Emerging drugs for treatment of focal segmental glomerulosclerosis
AbstractBACKGROUND: Glomerulosclerosis represents the final stage of glomerular injury during the course of kidney disease and can result from a primary disturbance in disorders like focal segmental glomerulosclerosis or a secondary response to tubulointerstitial disease. Overall, primary focal glomerulosclerosis (FSGS), the focus of this review, accounts for 10-20% of patients of all ages who progress to end stage kidney disease. There are no FDA approved therapeutic options that effectively prevent or delay the onset of kidney failure. AREAS COVERED: Current immunosuppressive therapy and conservative management including inhibitors of the renin-angiotensin-aldosterone axis and sodium-glucose cotransporter are reviewed. FSGS is now recognized to represent a heterogeneous entity with multiple underlying disease mechanisms. Therefore, novel approaches targeting the podocyte cytoskeleton, immunological, inflammatory, hemodynamic and metabolic pathways are highlighted. EXPERT OPINION: A number of factors are driving the development of drugs to treat focal segmental glomerulosclerosis in particular and glomerulosclerosis in general including growing awareness of the burden of chronic kidney disease, improved scientific understanding of the mechanism of injury, and the development of noninvasive profiles to identify subgroups of patients with discrete mechanisms of glomerular injury.
A case of dasatinib-induced focal segmental glomerulosclerosis in a patient with Philadelphia chromosome positive chronic myeloid leukemia
AbstractFocal segmental glomerulosclerosis is a common glomerular histological lesion, which is usually characterised by non-nephrotic range proteinuria or nephrotic syndrome. It may be idiopathic or occurs secondarily to drugs, diabetes, obesity or HIV nephropathy and other infections. Dasatinib, a tyrosine kinase inhibitor that has been used for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, has a few renal adverse effects. Exceptional cases with non-nephrotic range proteinuria have been reported in relation with dasatinib. In this case, we report a patient with symptoms of nephrotic syndrome and nephrotic range proteinuria, who was diagnosed as focal segmental glomerulosclerosis by kidney biopsy after treated with dasatinib.
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.
NIDDK Central Repository Resources for Research (NIDDK-CR R4R) · 2021 · 0 citations · open access
Novel Therapies to Treat Resistant Focal Segmental Glomerulosclerosis: Phase II Clinical Trial
AbstractTherapeutic interventions for the treatment of Focal Segmental Glomerulosclerosis Clinical (FSGS) have been widely reported. However, evidence-based treatment guidelines have not been developed because of the lack of controlled studies and the small number of participants included in most reports. The FSGS Clinical Trial (FSGS-CT) was a multi-center, prospective, controlled, open label randomized trial designed to determine if treatment with mycophenolate mofetil (MMF) in conjunction with pulse steroids is superior to treatment with Cyclosporine-A (CSA) in inducing remission from proteinuria over 12 months. The rationale and background related to each of the drugs chosen to be a part of the FSGS-CT therapeutic interventions are outlined in the study protocol.
Kidney International Reports · 2024 · 0 citations · open access
WCN24-281 A STUDY ON THE FACTORS AFFECTING OUTCOMES OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS AND THE IMPORTANCE OF GENETIC DIAGNOSTICS IN PREDICTING OUTCOMES
AbstractFocal segmental glomerulosclerosis(FSGS) is a histologic lesion primarily affecting podocytes. Age of onset, proteinuria at onset, plasma creatinine at biopsy, duration of treatment with corticosteroids, genetics and histopathologic subtype are important prognostic factors in determining the outcome of primary FSGS. Genetic causes of FSGS are often underdiagnosed in India. Genetic analysis in FSGS have implications on prognostication, therapy, transplantation and preimplantation genetic diagnosis.
Diagnosis and primary care management of focal segmental glomerulosclerosis in children
AbstractFocal segmental glomerulosclerosis (FSGS) is a pattern of kidney damage that can occur in individuals at any age, including children. Pediatric patients with FSGS require medication monitoring, growth, and psychological health. This article discusses the NP's role in the clinical presentation, diagnostic workup, and treatment of FSGS in pediatric patients.
Abstracthe term “focal segmental glomerulosclerosis” is used to describe the common morphologic lesion underlying various progressive renal diseases and also to deseribe the clinical syndrome of nephrotic syndrome with occurrence of the primary idiopathic lesion of focal segmental glomerulosclerosis. Thus, focal segmental glomerulosclerosis is not one disease but rather a term that describes a range of lesions seen in many settings. Specific morphologic variants of the sclerotic lesions and the patient's unique genetic factors contribute to prognosis, and also may dictate choice of optimum therapy. Morphologic features are described that aid in distinguishing various sclerotic lesions.
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.
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