DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Waardenburg syndrome type 4C — 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 moduleWaardenburg syndrome type 4C 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 waardenburg syndrome type 4c 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
RNA polymerase II, I and III subunit F (POLR2F) — POLR2F 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 sf4drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7AE1 · 2.8 Å · ligand IRON/SULFUR CLUSTER (SF4). Experimental structure, not a prediction.
What the evidence adds up to
Waardenburg syndrome type 4C is a rare inherited disorder. A study of 620 students in a deaf/blind school in Nigeria found four cases, a frequency of 0.65%. All four had complete blue irides, white forelock, and sensorineural hearing loss ranging from severe to profound; one was stone deaf. Two of the four benefited from amplification and were given hearing aids. The authors note the syndrome may be under-reported in that environment.
Genetic analysis of seven patients with Waardenburg syndrome detected mutations in all seven. Four mutations in the PAX3 gene and one in the SOX10 gene had not been reported previously. Three non-synonymous single nucleotide polymorphisms were predicted to be harmful. In a separate family study, a c.763C>T mutation in the MITF gene was identified. In laboratory experiments, the mutant MITF protein showed aberrant localisation in both the nucleus and the cytoplasm, whereas the wild-type protein localised only in the nucleus. The authors suggest this mislocalisation may be part of the molecular mechanism.
An earlier review of 27 subjects with a family history of Waardenburg syndrome examined 18 specific characteristics and concluded that patients may have a variety of clinical signs, making accurate diagnosis dependent on a thorough family history and physical examination. No drug treatment for the syndrome itself is mentioned in any of these abstracts.
What is still missing is any clinical trial of a drug for Waardenburg syndrome type 4C, any evidence that a drug can alter the course of the hearing loss or pigmentary features, and any patient stratification beyond genetic mutation type. Funding for preclinical work on the molecular pathways, or for a trial design that could test a repurposed agent, has not been reported.
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.
Nigerian Journal of Medicine · 2010 · 3 citations · open access
Audiometric Findings in Waardenburg's Syndrome Amongst the Institutionalised Deaf / Blind in Kaduna-Nigeria
AbstractINTRODUCTION: Waardenburg's syndrome is a rare inherited disorder of congenital hearing loss and Pigmentary disturbances of the eyes, hair, skin and neural crest derivatives. METHODOLOGY: 620 students in a deaf/blind school were examined end four had Waardenburg's syndrome with a frequency of 0.65%. 2 males and 2 females with Waardenburg's syndrome and age ranges between 1019 years (mean 15.75 years) All 4 subjects had complete blue irides, white forelock and sensorineural hearing loss, and thus met the diagnostic criteria. They were then subjected to Audiometric assessment. RESULTS: Otoscopy was essentially normal but Audiometry revealed sensorineural hearing loss [SNHL] in all the subjects ranging from severe to profound with one subject being stone deaf. CONCLUSION: Waardenburg's syndrome is a rare disorder in our environment although it may be under reported. Two of the subjects benefited from amplification and were given hearing Aids. Provision of early amplification cannot be over emphasized.
[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.
A Rare Syndromic Case of Total Colonic Aganglionosis
AbstractWaardenburg syndrome (WS) is a rare hereditary disorder characterised by varying degree of sensorineural hearing loss, pigmentary disorders and disorders in the structures arising from neural crest. Four different types of WS have been described: Types I and II are most common whereas Types III and IV (or Waardenburg–Shah syndrome) are rare. We report a case summary of Waardenburg–Shah syndrome in a 1-year-old child.
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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