DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Denys-Drash syndrome — 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 moduleDenys-Drash syndrome 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 denys-drash syndrome 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
WT1 transcription factor (WT1) — WT1 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 6BLW · 1.835 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A single case report from 2010 describes a patient with Denys-Drash syndrome in whom cyclosporin A induced total remission of proteinuria. The authors state that diffuse mesangial sclerosis is commonly assumed unresponsive to any medication, and they confirm a beneficial effect of cyclosporin A in this one patient. They also note that the potential nephrotoxicity of the drug will probably not allow long-term use. No other drugs are mentioned in the abstracts for Denys-Drash syndrome.
A 1996 report identifies a previously undescribed WT1 gene mutation (366Arg to Leu substitution in exon 8) in an 11-month-old boy with hypospadias, bilateral undescended testes, and renal failure but no Wilms' tumour. A 2006 case report of Frasier syndrome, a related WT1 mutation disorder, describes a patient who became dialysis-dependent due to focal sclerosing glomerulonephritis and received a kidney transplant, followed by prophylactic castration for gonadal blastoma risk. That report recommends prophylactic castration for male patients with confirmed Frasier syndrome and loss of testicular function, and suggests that phenotypic females with focal sclerosing glomerulonephritis be examined for WT1 mutations.
The evidence for Denys-Drash syndrome consists of a single case of cyclosporin A response and a handful of genetic reports. No controlled trials exist. What is missing is any systematic trial of cyclosporin A or other immunosuppressants, long-term safety data in this specific population, and any stratification by mutation type or disease stage.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Pediatrics · 2010 · 20 citations · open access
Effect of cyclosporin A on proteinuria in the course of glomerulopathy associated with WT1 mutations
AbstractDenys-Drash syndrome (DDS) is characterized by progressive glomerulopathy caused by diffuse mesangial sclerosis (DMS), genitourinary defects, and a higher risk of developing Wilms' tumor. It is commonly assumed that the DMS is unresponsive to any medications. In this report, we present a patient with Denys-Drash syndrome, in whom the cyclosporine A (CsA) was found to induce total remission. This observation and observations of other authors confirm that in genetic forms of nephrotic syndrome, the proteinuric effect of CsA may be due to a non-immunologic mechanism. We confirm the beneficial effect of CsA treatment in DDS; however, the potential nephrotoxicity of this drug will probably not allow long-term use.
Frasier-Syndrom: Ein seltenes Syndrom mit WT1-Genmutation in der Kinderurologie
AbstractINTRODUCTION: Frasier syndrom is an autosomal dominant, hereditary disease characterized by nephropathy, gonadal dysgenesis and risk of gonadal blastoma in early childhood. To date, in many patients with Frasier syndrome WT1 mutations have been found, occurring exclusively as germ-line mutations of the alternative splicing donor site in intron 9. A Wilms tumor is seen only rarely in this clinical entity. In the present paper we describe the clinical course of a patient with Frasier syndrome confirmed by molecular genetic analysis. CASE REPORT: Our patient with Frasier syndrome as confirmed by molecular genetic analysis is now 19 years old. The patient became dependent on dialysis due to nethropathy in the form of focal sclerosing glomerulonephritis and terminal renal insufficiency. A kidney transplantation in the left iliac fossa together with new implantation of the ureter according to Dodson. For prophylactic reasons on account of the high risk of gonadal blastoma associated with the disease and sonographically detected microlithiasis in both testicles we performed one year later an inguinal castration. Histology revealed the picture of a severe tubular testicular atrophy with arrested spermatogenesis and focal intratubular germ-line neoplasia. CONCLUSIONS: This case report shows that, besides our already published series with Denys-Drash syndrome, WT1 mutations may also be associated with the so-called Frasier syndrome. For children with Frasier syndrome confirmed by molecular genetic analysis and loss of function of the testicles, we recommend performance of a prophylactic castration. We also suggest that phenotypical female patients with focal sclerosing glomerulonephritis be examined for WT1 mutations.
A newly identified exonic mutation of the WT1 gene in a patient with Denys‐Drash syndrome
AbstractAn 11 month old boy with hypospadias and bilateral undescended testes developed renal failure. Denys-Drash syndrome was suspected and molecular analysis of the WT1 gene was performed, although no Wilms' tumor was identified. Direct sequencing analysis of genomic DNA from this patient revealed a G to A transition resulting in 366Arg to Leu substitution in exon 8 which has hitherto not been described. This newly identified mutation will help in the understanding of functional domains and in making a diagnosis of Denys-Drash syndrome.
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.
