DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for renal coloboma 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 moduleRenal coloboma 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 renal coloboma 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.
What the evidence adds up to
Renal coloboma syndrome is an autosomal dominant genetic disorder caused by mutations in the PAX2 gene. In one family, at least 7 members showed manifestations of the syndrome, with a pathogenic frame-shift mutation (619insG) found in affected individuals, who displayed remarkable variability in both ocular and renal features. A separate family with a different PAX2 mutation (exon 2; NM_003987.3:c.76dupG, p.Val26Glyfs*28) also showed diverse renal phenotypes: the proband had steroid-resistant focal segmental glomerulosclerosis with optic coloboma, while his two sons had severe renal hypoplasia with end-stage renal disease, with or without optic coloboma. Approximately 10% of children with hypoplastic kidneys may have renal coloboma syndrome.
The syndrome primarily affects kidney and eye development. Kidneys are typically small and underdeveloped (hypodysplastic), which can lead to end-stage renal disease. Eye anomalies consist of a wide and dysplastic optic disk with retinal vessels emerging from the periphery of the disk, frequently called optic nerve coloboma. Retinal detachment and decreased visual acuity are implications of the ocular malformations. Hypertension, proteinuria, and renal insufficiency are serious consequences of renal dysplasia. One case report described a neonate with multicystic dysplastic kidney and coloboma of the right eye, making a probable diagnosis of renal coloboma syndrome. In the family with the c.76dupG mutation, researchers hypothesised that autophagic dysfunction was associated with the pathophysiology of the focal segmental glomerulosclerosis seen in the proband.
A 2022 review summarised that 5–8% of renal tumours are hereditary, often autosomal-dominant, and that advances in treatment have been achieved through understanding the genetic renal neoplasia syndromes. That review did not specifically address renal coloboma syndrome. No treatment or drug is mentioned in any of the abstracts for renal coloboma syndrome itself. The abstracts provide no data on survival, response rates, or sample sizes beyond the small family and case reports described.
What is still missing is any clinical trial testing a drug for renal coloboma syndrome, any funded research into pharmacological intervention, and any patient stratification strategy that might identify which individuals with PAX2 mutations progress to end-stage renal disease and which do not.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics · 2001 · 44 citations
Renal-coloboma syndrome: Prenatal detection and clinical spectrum in a large family
AbstractRenal-coloboma syndrome includes abnormalities in the urogenital and ocular systems as its primary manifestations, although it can be associated with abnormalities in other systems as well. This syndrome is caused by mutations in the PAX2 gene and is transmitted as an autosomal dominant trait. We report a family in which at least 7 members have manifestations of renal-coloboma syndrome, including two in whom renal disease was diagnosed prenatally by ultrasound examination. A pathogenic frame-shift mutation (619insG) was found in the PAX2 gene in affected family members, who show remarkable variability in both the ocular and renal manifestations of the syndrome.
Internal Medicine · 2015 · 33 citations · open access
Minimal Change Nephrotic Syndrome Associated with Gefitinib and a Successful Switch to Erlotinib
AbstractMinimal change nephrotic syndrome (MCNS) is a common form of nephrotic syndrome (NS). We herein present the case of a 57-year-old woman with advanced lung adenocarcinoma treated with the tyrosine kinase inhibitor (TKI) gefitinib who developed NS. A renal biopsy revealed minor glomerular abnormalities, and the patient's symptoms improved exclusively with the discontinuation of gefitinib. Therefore, we diagnosed her with MCNS associated with gefitinib treatment. A few months later, however, she developed recurrent lung tumors. Following the challenging initiation of the TKI erlotinib, she achieved remission without proteinuria. We thus conclude that erlotinib is a potential treatment option in patients with NS associated with gefitinib therapy.
Case Reports in Nephrology and Dialysis · 2016 · 16 citations · open access
Diverse Renal Phenotypes Observed in a Single Family with a Genetic Mutation in Paired Box Protein 2
AbstractA common renal phenotype of paired box protein 2 (PAX2) mutations is renal coloboma syndrome. We report a single family with diverse renal phenotypes associated with PAX2 mutation. The proband presented steroid-resistant focal segmental glomerulosclerosis with optic coloboma, whereas his two sons showed severe renal hypoplasia with end-stage renal disease, with or without optic coloboma. In all three cases, a heterozygous PAX2 genetic mutation was identified (exon 2; NM_003987.3:c.76dupG, p.Val26Glyfs*28). Based on histopathological findings of the proband, we hypothesized that autophagic dysfunction was associated with the pathophysiology of the focal segmental glomerulosclerosis with PAX2 mutation. Detailed funduscopic examination - including the optic disc - might be useful for the diagnosis of renal anomalies associated with PAX2 mutation.
The pathological and molecular genetic landscape of the hereditary renal cancer predisposition syndromes
AbstractIt is estimated that 5-8% of renal tumours are hereditary in nature, with many inherited as autosomal-dominant. These tumours carry a unique spectrum of pathological and molecular alterations, the knowledge of which has expanded in recent years. Due to this knowledge, many advances in the treatment of these tumours have been achieved. In this review, we summarize the current understanding of the genetic renal neoplasia syndromes, clinical and pathological presentations, molecular pathogenesis, advances in therapeutic implications and targeted therapy.
Dasatinib-Induced Nephrotic Syndrome: A Case Report
AbstractSecond-generation tyrosine kinase inhibitors (TKI), such as nilotinib and dasatinib, are used in the first-line treatment of chronic myeloid leukemia (CML), usually after the failure or resistance to imatinib. Despite a good safety profile, medications in this category have an increased incidence of specific adverse events such as pulmonary hypertension, pleural effusion, and cardiovascular/peripheral arterial events. However, renal complications are rarely reported and observed. We herein report a case of a 46-year-old patient with CML who developed nephrotic syndrome upon switching from imatinib to dasatinib therapy, with the resolution of symptoms upon treatment discontinuation and switching to nilotinib. Limited cases were reported in the literature. It is thought that the inhibition of the vascular endothelial growth factor (VEGF) pathway is the main mechanism leading to proteinuria. Dasatinib-induced nephrotic syndrome should be looked for as it can be resolved by either reducing the dose or stopping it altogether and switching to another TKI.
Pseudohypoglycaemia in Acute Renal Failure with Wernicke-Korsakoff Syndrome
AbstractLetters| December 03 2008 Pseudohypoglycaemia in Acute Renal Failure with Wernicke-Korsakoff Syndrome Subject Area: Nephrology P. Stratta; P. Stratta Cattedra di Nefrologia Medica e di Search for other works by this author on: This Site PubMed Google Scholar C. Canavese; C. Canavese Cattedra di Nefrologia Medica e di Search for other works by this author on: This Site PubMed Google Scholar A. Robecchi; A. Robecchi Clinica Chirurgica dellUniversità di Torino, Search for other works by this author on: This Site PubMed Google Scholar Q. Carta; Q. Carta Centra Antidiabetico, Servizi di Search for other works by this author on: This Site PubMed Google Scholar E. Luda; E. Luda Neurologia e di Search for other works by this author on: This Site PubMed Google Scholar F. Balzola; F. Balzola Dietologia dell'Ospedale Maggiore di San Giovanni Battista e della Città di Torino, Italia Search for other works by this author on: This Site PubMed Google Scholar A. Vercellone A. Vercellone Cattedra di Nefrologia Medica e di Search for other works by this author on: This Site PubMed Google Scholar Nephron (1982) 31 (1): 94–95. https://doi.org/10.1159/000182624 Article history Accepted: December 14 1981 Published Online: December 03 2008 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation P. Stratta, C. Canavese, A. Robecchi, Q. Carta, E. Luda, F. Balzola, A. Vercellone; Pseudohypoglycaemia in Acute Renal Failure with Wernicke-Korsakoff Syndrome. Nephron 1 January 1982; 31 (1): 94–95. https://doi.org/10.1159/000182624 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsNephron Search Advanced Search This content is only available via PDF. 1982Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Article PDF first page preview Close Modal You do not currently have access to this content.
Indian journal of radiology and imaging - new series/Indian journal of radiology and imaging/Indian Journal of Radiology & Imaging · 2023 · 1 citations · open access
AbstractRenal coloboma syndrome is an autosomal dominant genetic disorder that primarily affects kidney and eye development. It is also known as papillorenal syndrome. People with this condition typically have kidneys that are small and underdeveloped (hypodysplastic), which can lead to end-stage renal disease. It has been estimated that approximately 10% of children with hypoplastic kidneys may have renal coloboma syndrome. The eye anomalies consist of a wide and dysplastic optic disk with the emergence of the retinal vessels from the periphery of the disk, frequently called optic nerve coloboma.
Case Reports in Clinical Radiology · 2023 · 0 citations · open access
A rare case report: Renal coloboma syndrome
AbstractRenal coloboma syndrome (RCS), also called papillorenal syndrome, is a rare syndrome characterized by renal abnormalities and optic nerve dysplasia. We present a case of a neonate with renal and eye abnormalities. Along with the known diagnosis of multicystic dysplastic kidney, the neonate was diagnosed with coloboma of the right eye, making a probable diagnosis of RCS. Retinal detachment and decreased visual acuity are implications of the ocular malformations. Hypertension, proteinuria, and renal insufficiency, which frequently lead to end-stage kidney disease, are serious consequences of renal dysplasia.
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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