DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Waardenburg syndrome type 1 — screening already-approved drugs against its 5-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 1 maps to a 5-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 1 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 1 is an autosomal dominant disorder. About 20% of affected individuals are deaf. The syndrome consists of six major features that may appear in any combination and to any degree in the affected person. Because the condition is inherited dominantly, there is a risk of it being handed down from generation to generation.
A four-generation family with WS1 was found to carry a G to C transversion in PAX3 exon 7, a glutamine to histidine missense mutation at position 391 that may also affect splicing. This was the first WS1 mutation reported in exon 7 of PAX3, among over 50 mutations then characterised in PAX3 in WS1 patients. The proband in that family exhibited both WS1 and septo-optic dysplasia.
In a separate study of seven patients with Waardenburg syndrome, genetic mutations were detected in all seven. Seven mutations were identified, including four in PAX3 (c.72delG, c.185T>C, c.118C>T, c.128G>T) and one in SOX10 (c.422T>C) that had not been reported previously. Three non-synonymous SNPs were predicted as harmful. In another family, a c.763C>T mutation of the MITF gene was identified. In vitro, the mutant R255X MITF protein showed aberrant localisation in both the nucleus and the cytoplasm, whereas wild-type MITF protein localised only in the nucleus.
No drug, treatment, or intervention for Waardenburg syndrome type 1 is mentioned in any of these abstracts. What is still missing is any clinical trial, any attempt at pharmacological intervention, any patient stratification beyond genetic diagnosis, and any funding directed toward treatment rather than mutation discovery.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Medical Genetics · 1998 · 21 citations · open access
Septo-optic dysplasia and WS1 in the proband of a WS1 family segregating for a novel mutation in PAX3 exon 7.
AbstractA four generation family (UoM1) was ascertained with Waardenburg syndrome type 1 (WS1). The proband exhibited both WS1 and septo-optic dysplasia. A G to C transversion was identified in PAX3 exon 7 in four subjects affected with WS1 in this family including the proband. This glutamine to histidine missense mutation at position 391 may also affect splicing. There are over 50 mutations characterised in PAX3 in WS1 patients; however, this is the first example of a WS1 mutation in exon 7 of PAX3.
[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.
Waardinburg syndrome — inherited deafness with pigmentary involvement
AbstractThe Waardenburg syndrome was first clearly defined in 1951. The major clinical importance lies in the fact that about 20% of affected individuals are deaf. Furthermore, because the condition is inherited autosomal dominantly, there is a risk of the disorder being handed down from generation to generation. The syndrome consists of six major features which may appear in any combination and to any degree in the affected individual.
International Journal of Research Publications · 2022 · 0 citations · open access
Waardenburg Syndrome Type 1: A Case Report
AbstractAs a result of the deficiency of melanocytes in the hair, skin, and eyes, Waardenburg syndrome is an extremely uncommon hereditary condition. Clinical aspects, such as major and minor criteria, are often used to make a diagnosis based on a patient's symptoms and signs. An infant with Waardenburg syndrome type 1 had a white forelock, sensorineural hearing loss, depigmented macules on the skin, and premature graying hair.
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.
