DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for acute proliferative glomerulonephritis — 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 moduleAcute proliferative glomerulonephritis 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 acute proliferative glomerulonephritis 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
Rac family small GTPase 2 (RAC2) — RAC2 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1DS6 · 2.35 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
In a 1972 review, the pathogenesis of glomerulonephritis was described as involving immune mechanisms, particularly chronic soluble complex deposition in the kidney, but non-immunological origins and mediation of injury were considered at least as important. Injury to the glomerulus was understood to be mediated through the interaction of complement and coagulation mechanisms, leading to inflammation. Treatment at that time could be directed toward the immediate mediators of injury, but the author noted that better identification of the events leading to injury in individual patients was needed, such as isolating or eliminating the antigens involved in chronic soluble complex disease. No specific drug or treatment outcome data were reported.
By 1999, crescentic glomerulonephritis was described as a therapeutic challenge because of its rapidly progressive course and poor outcome. Studies in animal models had elucidated some pivotal pathogenetic mechanisms, and human studies increasingly supported the clinical relevance of these animal data. The accumulating evidence suggested that crescentic glomerulonephritis results from a complex cell-mediated nephritogenic immune response, and that interruption of a number of immune and inflammatory mediators could improve the outcome of this disease. No concrete survival or response rates were given.
A 2009 review stated that although the rationale for an etiological treatment of primary glomerulonephritis was still lacking, some clinical studies had shown that certain subtypes might benefit from empirical treatment based on glucocorticoids or immunomodulating agents. The chapter reviewed the clinical pharmacology, mechanisms of action, and toxic effects of these drugs, but no specific efficacy numbers or trial results were provided.
A 2011 review noted that glomerulonephritis is a major cause of chronic kidney disease worldwide and presents with various histological and clinical manifestations, resulting in diverse clinical outcomes. Immune-mediated injury of resident glomerular cells plays a critical role, and mounting evidence indicates that both humoral and cell-mediated mechanisms are involved. No treatment recommendations or outcome data were presented. What remains missing across these decades of research are adequately funded clinical trials that can stratify patients by the specific immune or non-immune mechanisms driving their disease, and a trial design that tests targeted interventions against those mechanisms rather than relying on empirical immunosuppression.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BMJ · 1972 · 42 citations · open access
Bright's Disease Today: The Pathogenesis and Treatment of Glomerulonephritis--I
AbstractSince Bright's day the study of glomerulonephritis has largely consisted in the observation of the clinical, biochemical, and morphological characteristics of patients. Linked to this has been the attempt to name and classify these data in a fashion which improved prediction of outcome and response to treatment. This has proved difficult, since there is no absolute correspondence between clinical syndromes and the morphological findings in the kidney. The histological data have, however, allowed good prediction of prognosis and response.We now have enough information from experimental models of nephritis and from clinical observation to outline the pathogenesis of glomerulonephritis. Immune mechanisms are certainly concerned in some patients, the role of chronic soluble complex deposition in the kidney being particulary important. Non-immunological origins and mediation of injury, however, are at least as important. Injury to the glomerulus is mediated through the interaction of complement and coagulation mechanisms, leading through the release of soluble factors to inflammation. Repair is probably central in producing irreversible glomerular damage.Treatment can now be directed towards the events concerned in the pathogenesis of nephritis, the most accessible at the moment being the immediate mediators of injury. At a more fundamental level better identification in individual patients of the events leading to the injury is needed, such as the isolation, avoidance, or elimination of the antigens involved in chronic soluble complex disease. Laboratory techniques to begin these investigations in man are now available and need to be applied more widely in the clinical field to patients with glomerulonephritis.
Current Opinion in Nephrology & Hypertension · 1999 · 32 citations
Immunopathogenesis of crescentic glomerulonephritis
AbstractCrescentic glomerulonephritis provides an important therapeutic challenge because of its rapidly progressive course and poor outcome. Studies in animal models have elucidated some of the pivotal pathogenetic mechanisms, and human studies increasingly support the clinical relevance of these animal data. Accumulating evidence suggests that crescentic glomerulonephritis results from a complex cell-mediated nephritogenic immune response. Interruption of a number of immune and inflammatory mediators can improve the outcome of this disease.
Oxford University Press eBooks · 2009 · 4 citations
Glucocorticoids and immunomodulating agents
AbstractAlthough the rationale for an etiological treatment of primary glomerulonephritis is still lacking, a number of clinical studies have shown that some subtypes of these diseases may benefit from empirical treatment based upon the use of glucocorticoids or immunomodulating agents. In this chapter the clinical pharmacology, the mechanisms of action, and the toxic effects of these drugs will be reviewed.
The Role of Humoral and Cell-Mediated Adaptive Immune Response
AbstractGlomerulonephritis is a major cause of chronic kidney disease worldwide and presents with various histological and clinical manifestations in terms of severity and duration, resulting in diverse clinical outcomes. Immune-mediated injury of the resident glomerular cells plays a critical role in many forms of glomerular injury and mounting evidence indicates that both humoral and cell-mediated mechanisms are involved.
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.
