DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cholesteatoma — 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 moduleCholesteatoma 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 cholesteatoma 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
serpin family C member 1 (SERPINC1) — SERPINC1 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 z9ldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3KCG · 1.7 Å · ligand methyl 2,3,6-tri-O-sulfo-alpha-D-glucopyranoside (Z9L). Experimental structure, not a prediction.
What the evidence adds up to
Cholesteatoma is managed primarily through surgery, with canal wall-up, canal wall-down, and hybrid techniques all reported as successful in children. Second-look procedures remain important when recurrence is a concern. Newer innovations include endoscopic ear surgery and diffusion-weighted imaging. The principal goal is eradication of disease, and an individualized approach is paramount, especially given anatomical and social factors in paediatric patients.
The molecular events underlying cholesteatoma involve a complex network of signalling pathways during epidermal hyperplasia, perimatrix-matrix interactions, and mucosal disease. Inflammatory mediators and enzymes drive cell proliferation and apoptosis, angiogenesis and hypoxia, oxidative stress and toxicity, and bone erosion and hearing loss. The role of lipids in this disease is relatively unexplored, though there is evidence supporting fatty acid involvement that needs confirmation.
RNA-Seq analysis of tissue-resident macrophages from cholesteatoma patients found 145 of 7060 genes significantly up-regulated compared to patients without cholesteatoma. These over-expressed genes indicated boosted inflammatory and anti-infection functions, including neutrophil function, leukocyte migration, and adaptive immune response pathways. Homeostasis and repair functions were affected by up-regulated genes such as over-expressed keratin-13 and MMPs, which promote inflammation and disturb tissue remodelling. Additionally, 74 down-regulated genes affected extracellular matrix structure and contractile fibres in these macrophages.
A 2025 review describes a paradigm shift from a primarily surgical solution to a biological "control and prevent" strategy, but no drug therapy has been tested in patients. What is still missing is any clinical trial of a molecularly targeted treatment, the funding to move from gene expression and pathway descriptions to a therapeutic candidate, and a way to stratify patients by the specific molecular drivers of their disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Otolaryngology & Head & Neck Surgery · 2013 · 55 citations
Management of acquired cholesteatoma in the pediatric population
AbstractPURPOSE OF REVIEW: This review focuses on the most recent literature pertaining to pediatric acquired cholesteatoma and aims to integrate findings into a comprehensive management approach. RECENT FINDINGS: Pediatric acquired cholesteatoma has been shown to differ from the adult variety secondary to anatomy and physiologic factors. Whereas the goals of therapeutic management are ultimately similar in adult and pediatric patients, special considerations must be taken into account when deciding on a treatment plan for a child. Although avoidance of an unstable mastoid cavity is an important consideration in this population, successful management has been reported with canal wall-up, canal wall-down, and hybrid techniques. Second-look procedures are also important when concern of recurrence exists. Newer innovations include endoscopic ear surgery and diffusion-weighted imaging. SUMMARY: The principal goal of pediatric cholesteatoma management is eradication of disease. An individualized approach is paramount in yielding superior results in these patients. Special consideration should be given to anatomical and social factors.
The Journal of Laryngology & Otology · 2013 · 41 citations
Acquired cholesteatoma: summary of the cascade of molecular events
AbstractBACKGROUND: Cholesteatoma is considered a benign, gradually expanding and destructive epithelial lesion of the temporal bone. The pathogenesis of different classifications of cholesteatoma is marked by similar underlying cellular and molecular processes. Stepwise explanations of the histopathogenesis have been described previously. The current paper focuses on expounding the molecular events of cholesteatoma. METHOD AND RESULTS: Cholesteatoma pathogenesis encompasses a complex network of signalling pathways during: epidermal hyperplasia, perimatrix-matrix interactions and mucosal disease. This paper presents a review of the molecular events driven by inflammatory mediators and enzymes during: cholesteatoma growth (cell proliferation and apoptosis); maintenance and deterioration (angiogenesis and hypoxia, oxidative stress and toxicity); and complications (bone erosion and hearing loss). The cascade of molecular events applicable to atelectasis and cholesteatoma that coexist with chronic otitis media and bone erosion as sequelae is summarised. CONCLUSION: The role of lipids in this disease is relatively unexplored, but there is evidence in support of fatty acid role-players that needs confirmation. Future directions in lipid research to delineate molecular mechanisms are proposed.
Analysis of Inflammatory and Homeostatic Roles of Tissue-resident Macrophages in the Progression of Cholesteatoma by RNA-Seq
AbstractBACKGROUND: Tissue-resident macrophages (TRMØs) can act as innate-immune sentinels to protect body against microbe invaders and stimulating materials such as cholesterol crystals in cholesteatoma, as well as to preserve tissue integrity by cleaning unwanted cellular debris. METHODS: TRMØs in the incised middle ear tissues were obtained from the patients with cholesteatoma as an experimental group and the patients without cholesteatoma as a control group. Differential gene expression profiling of TRMØs was conducted between two groups by analyzing GO processes, KEGG and GSEA pathways of inflammation, tissue repair and homeostasis. RESULTS: The current study showed that 145 of 7060 genes were significantly up-regulated (logFC>2 and FDR <0.05) when compared with the patients without cholesteatoma. GO process, GSEA and Cytoscape analysis of the over-expressed genes illustrated the boosted inflammatory and anti-infection functions of TRMØs existed neutrophil function, leukocyte migration, and adaptive immune response involved receptors and signaling pathways. Whereas the homeostasis and repair functions of TRMØs were affected from up-regulated genes, such as over-expressed keratin-13 that helped form the outer keratinising squamous epithelial layer, and over-expressed MMPs that activated the extracellular matrix molecules to promote inflammation and disturb tissue remodeling. Additionally, 74 down-regulated genes (logFC<-2 and FDR <0.05) also affected the homeostasis and repair functions by affecting extracelluar matrix structure and contractile fibres in TRMØs. CONCLUSIONS: The cellular and molecular levels in cholesteatoma is attributable to chronic infection and several disturbed cellular biological processes involving cell integrity and tissue remodeling.
International Journal of Molecular Sciences · 2025 · 2 citations · open access
Emerging Paradigms in Cholesteatoma: From a Traditional Approach to Personalized Therapy
AbstractCholesteatoma is a prevalent disease affecting both children and adults. In this review, we present the recent findings related to the molecular mechanisms involved in cholesteatoma and discuss how researchers can target new molecules to treat this disease. These new approaches illustrate the paradigm shift from a primarily surgical solution to a biological "control and prevent" strategy.
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.
