DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephrosis — 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 moduleNephrosis 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 nephrosis 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
polycystin 1, transient receptor potential channel interacting (PKD1) — PKD1 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 1rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ZKH · 2.3 Å · ligand (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl
(9Z)-octadec-9-enoate (PGW). Experimental structure, not a prediction.
What the evidence adds up to
In a 2017 retrospective study of 40 children with idiopathic nephrotic syndrome in Dakar, 77% (30 patients) were corticosensitive and 13% (5 patients) were corticoresistant. The overall remission rate was 89.8%. The only factor associated with poor response to corticosteroid therapy was initial proteinuria greater than 150 mg/kg/day (p = 0.024). Renal biopsy in 7 patients showed focal and segmental hyalinosis in 57.2% (4 patients). Cyclophosphamide and azathioprine were each used in 10% (4 patients) of cases. Three patients evolved toward chronic renal failure.
A 2001 experimental study in rats with adriamycin-induced nephropathy found that urine nitrite levels were significantly increased and that numerous apoptotic cells appeared in tubulointerstitial areas, many of which were monocytes or macrophages. Treatment with aminoguanidine, an inhibitor of inducible nitric oxide synthase, reduced both urine nitrite and apoptosis to control levels and prevented impairment of renal vascular responses. The study did not test aminoguanidine in human nephrosis.
A 1926 report described treatment of nineteen attacks of generalised edema in seven patients with nephrosis, defined by marked albuminuria, edema and cholesterolemia without hypertension, hematuria or elevated blood nitrogen. A 1930 report claimed that in three cases, administration of thyroid extract produced marked and immediate disappearance of edema and reduction of albumin, whereas treatment of presumed infectious processes had no effect. A 1965 review summarised twenty years of paediatric practice without providing quantitative outcomes. A 2013 review of podocyte proteins noted that expression of nephrin and Neph3 is altered in human proteinuric diseases but did not test any therapeutic agent.
What is still missing: prospective trials of aminoguanidine or other nitric oxide pathway modulators in human nephrosis; validation of the 1930 thyroid extract observation in a controlled setting; and identification of biomarkers that predict which patients with high initial proteinuria will respond to corticosteroids or to alternative immunosuppressants.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Science · 2013 · 37 citations
Functions of the podocyte proteins nephrin and Neph3 and the transcriptional regulation of their genes
AbstractNephrin and Neph-family proteins [Neph1-3 (nephrin-like 1-3)] belong to the immunoglobulin superfamily of cell-adhesion receptors and are expressed in the glomerular podocytes. Both nephrin and Neph-family members function in cell adhesion and signalling, and thus regulate the structure and function of podocytes and maintain normal glomerular ultrafiltration. The expression of nephrin and Neph3 is altered in human proteinuric diseases emphasizing the importance of studying the transcriptional regulation of the nephrin and Neph3 genes NPHS1 (nephrosis 1, congenital, Finnish type) and KIRREL2 (kin of IRRE-like 2) respectively. The nephrin and Neph3 genes form a bidirectional gene pair, and they share transcriptional regulatory mechanisms. In the present review, we summarize the current knowledge of the functions of nephrin and Neph-family proteins and transcription factors and agents that control nephrin and Neph3 gene expression.
New England Journal of Medicine · 1965 · 31 citations
The Treatment of Nephrosis
AbstractTHIS review is based upon our practices and an evaluation of their results over a twenty-year experience in the treatment of children with nephrosis. Limitations of space make it necessary to omit many considerations of interest, but it is hoped that those included are the more important ones to practitioners handling the occasional case of this relatively uncommon disorder.It is necessary at the outset to define nephrosis since the term has a variety of connotations. In the context of the following discussion nephrosis will be taken to mean the usually idiopathic, acquired disorder occurring primarily in infants and children, . . .
Association of nitric oxide production and apoptosis in a model of experimental nephropathy
AbstractBACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible-NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis.
American journal of diseases of children · 1926 · 11 citations
THE TREATMENT OF NEPHROSIS
AbstractIn any disease of obscure etiology, the effect of various therapeutic measures may be of interest theoretically as well as clinically, because response to treatment may give clues to etiologic factors. It is with this in mind that this report of the treatment of nineteen attacks of generalized edema occurring in seven patients with nephrosis is given. The type of nephrosis considered is that characterized by the presence of marked albuminuria, edema and cholesterolemia, and by the absence of hypertension, hematuria and increase of the nitrogenous elements of the blood. <h3>REVIEW OF THE LITERATURE</h3> In the literature of the past ten years, it is not unusual to find reports of cases which have some of the characteristics of nephrosis, but typical cases such as those described by Epstein<sup>1</sup>are seldom found. Only two papers were found which reported more than one or two cases. Schwarz and Kohn<sup>2</sup>give
Pan African Medical Journal · 2017 · 8 citations · open access
Le syndrome néphrotique idiopathique (SNI) de l’enfant à Dakar: à propos de 40 cas
AbstractINTRODUCTION: This study aimed to analyze the diagnostic, therapeutic, and evolutionary features of nephrosis in children in a pediatric department in Dakar. METHODS: The study was carried out in the Department of Pediatrics at the Aristide Le Dantec Hospital. We conducted a retrospective study over a period of 3 years from 1 January 2012 to 31 December 2014. All patients aged 2-12 years with idiopathic nephrotic syndrome were included in the study. RESULTS: Forty cases of nephrosis were collected, that is to say a prevalence of 23% among patients with kidney disease treated in the Department of Pediatrics. The average age was 7.11 ± 3.14 years. 72.5% (n=29) of patients suffered from pure nephrotic syndrome. Lower limb edema was present in 100% of patients, oliguria in 55% (n=22) and high blood pressure (HBP) in 5% (n=2) of cases. Median proteinuria was 145,05 ± 85,54 mg/kg/24 hours. Median protidemia was 46,42 ±7.88 g/L and median albumin was 17.90 ± 7.15 g/L. Thirty nine patients were treated with prednisone-based corticosteroid therapy. Corticosensitivity was retained in 77% (n=30) patients and corticoresistance in 13% (n=5) of cases. The factor of poor response after corticosteroid therapy was initial proteinuria greater than 150 mg/kg/day (p = 0.024). Renal biopsy was performed in 18% (n=7) of patients which showed focal and segmental hyalinosis in 57.2% (n=4). Cyclophosphamide and azathioprine were associated with corticosteroids in 10% (n=4) of cases respectively. The overall remission rate was 89.8%. The evolution toward chronic renal failure was observed in three patients. CONCLUSION: Nephrosis accounted for almost one quarter of all cases of kidney disease treated in our Department. It has high overall remission rate. The only factor contributing to poor response after corticosteroid therapy was high levels of initial proteinuria. Focal and segmental hyalinosis was the most frequently found lesion diagnosed by renal biopsy.
AbstractIt is now generally considered that nephrosis is not primarily a kidney disease. Many observers have contended that the condition is due to a chronic infection caused by a staphylococcus present in the nasal sinuses or by some other upper respiratory infection and that the condition is controlled by appropriate treatment of the sinus disease or infection. Reports in confirmation of such observations may be found in the current literature. It is not my intention to present a discussion of the etiology of nephrosis. However, the fact that adequate treatment of the infectious processes in the three cases reported had no effect on the edema and albuminuria which characterize the disease, even though persisted in for long periods of time, whereas the administration of thyroid extract produced a marked and immediate response as manifested by the disappearance of the edema and the reduction of the albumin, seems to me to
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.
