DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hematuria, benign familial — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHematuria, benign familial maps to a 2-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 hematuria, benign familial 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 3 chain (COL4A3) — COL4A3 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 5NB0 · 2.7 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2017 review states that benign familial hematuria, also called thin basement membrane nephropathy, is caused by a heterozygous mutation in the COL4A3 or COL4A4 gene. The prognosis is good in childhood for patients who present with isolated hematuria without proteinuria and with normal renal function. However, the prognosis is poor in adulthood for some patients who develop proteinuria, hypertension, chronic renal failure, and end-stage kidney disease. The review recommends long-term follow-up, with checks every one to two years for hypertension, proteinuria, and renal impairment, and says treatment should include an angiotensin converting enzyme inhibitor to delay the onset of renal failure.
A 2019 study of three families with hematuria whose probands were initially diagnosed with IgA nephropathy found that the variant of the CFHR5 gene identified in one family was of uncertain significance, while two variants of the COL4A5 gene identified in the other two families were pathogenic. The probands of those two families were diagnosed with Alport syndrome. The study suggests that clinicians should examine genetic variants of familial hematuria associated genes in families with hematuria when the probands were diagnosed by clinical manifestations, renal pathology, and routine immunohistochemistry.
A 1988 letter notes agreement that when evaluating children with hematuria it is important to screen the index case and family members for idiopathic hypercalciuria as well as for benign familial hematuria, and states that whether the two conditions coexist in the same patients has not been studied.
What is still missing are prospective trials testing whether angiotensin converting enzyme inhibitors alter the long-term renal outcomes specifically in genetically confirmed benign familial hematuria, and studies that stratify patients by genotype, proteinuria level, and blood pressure to identify who benefits from treatment. The natural history from heterozygous COL4A3 or COL4A4 mutations to end-stage kidney disease in adulthood is not well quantified in large cohorts, and no randomised controlled trial has been conducted.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Urology · 2013 · 22 citations · open access
Hematuria Secondary to Benign Prostatic Hyperplasia: Retrospective Analysis of 166 Men Identified in a Single One Stop Hematuria Clinic
AbstractINTRODUCTION: Hematuria secondary to benign prostatic hyperplasia (BPH) can occur due to a vascular primary gland itself or due to the vascular re-growth of the prostate following a transurethral resection of the prostate (TURP). We aim to evaluate the clinical presentation and management in patients within both these groups. MATERIALS AND METHODS: We retrospectively archived the data of 166 men diagnosed with hematuria secondary to BPH from our hematuria clinic database from March 2003 and March 2006. The 166 patients were divided into 2 groups: Group I (n = 94) hematuria with no previous TURP; Group II (n = 72) hematuria with previous TURP. The clinical management in both groups included reassurance, commencement of a 5-alpha reductase inhibitor (finasteride) or a primary TURP in Group I or re-do TURP in Group II. RESULTS: The median age was 73 years (range 45-94 years) for both groups. Outcomes combined for both groups included: reassurance alone in 26% (n = 43), finasteride in 51% (n = 84) and TURP in 12% (n = 19). Patients managed with reassurance alone or TURP had no further episodes of hematuria. At a mean follow-up was 18 months (range 7-22 months), 2 patients treated with finasteride re-bled but did require further intervention. A further 2 men elected to stop finasteride due to erectile dysfunction and gynecomastia respectively. CONCLUSION: BPH can present with hematuria. Following re-evaluation in a hematuria clinic, the lack of any subsequent cancer diagnosis in these patients suggests that repeat hematuria investigations should be carefully re-considered.
[Genetic variants of familial hematuria associated genes in three families with hematuria with probands initially diagnosed as IgA nephropathy].
AbstractThe variant of the CFHR5 gene identified in Family One is of uncertain signifance, and the two variants of the COL4A5 gene identified in Families Two and Three are pathogenic. The probands of Families Two and Three are diagnosed as Alport syndrome. The study suggests that clinicians should examine genetic variants of FH associated genes in families with hematuria when the probands were diagnosed as IgAN by their clinical manifestations, renal pathology and routine immunohistochemistry.
Abstract<h3>In Reply.—</h3> We agree with Drs Zelikovic, Stapleton, and Chesney that when evaluating children with hematuria it is important to screen the index case and family members for idiopathic hypercalciuria as well as for benign familial hematuria. Whether benign familial hematuria and idiopathic hypercalciuria coexist in the same patients has not been studied.
AbstractBenign familial hematuria, also called thin basement membrane nephropathy, is caused by a heterozygous mutation in the COL4A3 or COL4A4 gene.The prognosis of the patients with benign familial hematuria, who present isolated hematuria without associated with proteinuria and normal renal function, is good in childhood.However, the prognosis of part of the patients with benign familial hematuria, who appear proteinuria, hypertension, chronic renal failure and end-stage kidney disease, is poor in adulthood.Therefore, the patients with benign familial hematuria should be carried on the long-term follow-up, and may be reviewed every 1-2 years for hypertension, proteinuria, and renal impairment.Treatment for benign familial hematuria should include an angiotensin converting enzyme inhibitor to delay the onset of renal failure.
Key words:
Benign familial hematuria; Thin basement membrane nephropathy; COL4A3 gene; COL4A4 gene
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.
