DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Waardenburg syndrome type 4A — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleWaardenburg syndrome type 4A maps to a 3-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 waardenburg syndrome type 4a 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
endothelin receptor type B (EDNRB) — EDNRB 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 2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6IGK · 2.0 Å · ligand (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate (OLC). Experimental structure, not a prediction.
What the evidence adds up to
Twenty-seven subjects with a family history of Waardenburg syndrome were examined in a 1981 study, which found that patients can present with a variety of clinical signs and that accurate diagnosis depends on thorough family history and physical examination. No drug or treatment was tested.
In a 2016 genetic analysis of seven patients with Waardenburg syndrome, seven mutations were detected across the PAX3, SOX10, MITF and SNAI2 genes. Four PAX3 mutations (c.72delG, c.185T>C, c.118C>T, c.128G>T) and one SOX10 mutation (c.422T>C) had not been reported previously. Three non-synonymous single nucleotide polymorphisms were predicted as harmful. No drug or treatment was tested.
A 2017 study of one family with Waardenburg syndrome identified a c.763C>T mutation in the MITF gene. In vitro experiments showed that the mutant MITF protein (R255X) localised aberrantly in both the nucleus and cytoplasm, whereas the wild-type protein localised only in the nucleus. No drug or treatment was tested.
A 1989 report described two mutations in the PAX3 gene causing Waardenburg syndrome type I in two families: an insertion in the paired box domain leading to protein termination, and a base pair substitution producing an arginine to cysteine change in the homeobox region. No drug or treatment was tested. What is still missing is any clinical trial of a drug for Waardenburg syndrome type 4A, any animal model testing of a repurposed compound, and any patient stratification based on specific mutations that might guide future treatment attempts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Otolaryngology · 1981 · 10 citations
Waardenburg's Syndrome: Variations in Expressivity
AbstractTwenty-seven subjects with a family history of Waardenburg's syndrome were examined with respect to 18 specific characteristics of the syndrome, with particular emphasis in identifying the spectrum of the phenotypic expression of affected persons. Our results indicate that patients with the syndrome may have a variety of clinical signs, and an accurate diagnosis will therefore depend on a thorough and pertinent family history and physical examination.
[Mutation analysis of seven patients with Waardenburg syndrome].
AbstractOBJECTIVE: To perform genetic analysis for 7 patients with Waardenburg syndrome. METHODS: Potential mutation of MITF, PAX3, SOX10 and SNAI2 genes was screened by polymerase chain reaction and direct sequencing. Functions of non-synonymous polymorphisms were predicted with PolyPhen2 software. RESULTS: Seven mutations, including c.649-651delAGA (p.R217del), c.72delG (p.G24fs), c.185T>C (p.M62T), c.118C>T (p.Q40X), c.422T>C (p.L141P), c.640C>T (p.R214X) and c.28G>T(p.G43V), were detected in the patients. Among these, four mutations of the PAX3 gene (c.72delG, c.185T>C, c.118C>T and c.128G>T) and one SOX10 gene mutation (c.422T>C) were not reported previously. Three non-synonymous SNPs (c.185T>C, c.128G>T and c.422T>C) were predicted as harmful. CONCLUSION: Genetic mutations have been detected in all patients with Waardenburg syndrome.
[Study of gene mutation and pathogenetic mechanism for a family with Waardenburg syndrome].
AbstractOBJECTIVE: To explore the pathogenetic mechanism of a family affected with Waardenburg syndrome. METHODS: Clinical data of the family was collected. Potential mutation of the MITF, SOX10 and SNAI2 genes were screened. Plasmids for wild type (WT) and mutant MITF proteins were constructed to determine their exogenous expression and subcellular distribution by Western blotting and immunofluorescence assay, respectively. RESULTS: were confirmed. Both proteins were detected with the expected size. WT MITF protein only localized in the nucleus, whereas R255X protein showed aberrant localization in the nucleus as well as the cytoplasm. CONCLUSION: The c.763C>T mutation of the MITF gene probably underlies the disease in this family. The mutation can affect the subcellular distribution of MITF proteins in vitro, which may shed light on the molecular mechanism of Waardenburg syndrome caused by mutations of the MITF gene.
Molecular and Cellular Probes · 1989 · 0 citations
Contribution à la connaissance de l'évolution géodynamique anté-varisque de la croûte continentale de la Péninsule ibérique par la géochronologie U/Pb sur zircons
AbstractWaardenburg syndrome (WS) is a form of autosomal dominant inherited deafness combined with specific congenital anomalies. WS types I and III are correlated with mutations in the PAX3 gene on chromosome 2q37. In this report we describe two mutations in the human PAX3 gene causing WS type I in two families. One mutation is an insertion in the paired box domain resulting in a protein termination within the paired box. The second mutation is a base pair substitution producing an arginine to cysteine amino acid change in the homeobox region.
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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