DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cholesteatoma of middle ear — 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 moduleCholesteatoma of middle ear 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 cholesteatoma of middle ear 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
MYC proto-oncogene, bHLH transcription factor (MYC) — MYC 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5I4Z · 1.95 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 2011 retrospective study of 30 patients aged 9 to 75 years who underwent exclusive endoscopic transmeatal cholesteatoma eradication between July 2008 and May 2010, no iatrogenic injuries to the facial nerve or ossicles were reported. Closure of the tympanic membrane and good hygienic status (water tolerance and absence of inflammation) were achieved in all operated ears. Two patients had significant postoperative worsening of sensorineural hearing loss: one whose cholesteatoma involved all three ossicles and the oval window, and another who experienced postoperative labyrinthitis. Among 18 patients followed for more than one year, there was no residual disease, and non-echo-planar diffusion-weighted MRI was negative in three patients.
The 2016 literature review covers definitions of middle ear cholesteatoma from V. F. Undrits, L. T. Levin, V. T. Palchun, I. Friedmann, H. Schuknecht and others, along with macroscopic and microscopic structure, existing classifications, and theories of etiology and pathogenesis for congenital and acquired forms. A 2019 review states that squamous epithelial hyperplasia, cell apoptosis and bone destruction are considered three key mechanisms in pathogenesis, and that various apoptosis-related genes and regulatory factors are associated with cholesteatoma development. Another 2019 review describes cholesteatoma as a destructing process due to non-self-limiting chronic proliferative inflammation, with possible consequences including hearing loss, vestibular dysfunction, facial nerve paralysis and intracranial complications; it notes that little is known about etiopathogenesis and that new studies focus on the innate immune system and the microbiome.
No drug treatment is mentioned in any of these abstracts. The therapy of choice remains surgical. What is still missing is a clear understanding of the molecular pathways that drive cholesteatoma formation and progression, and whether any pharmacological intervention could alter those pathways. No clinical trial has tested a drug for this condition. Patient stratification by genetic or immune markers has not been attempted. Funding for basic research into the innate immune system and microbiome in cholesteatoma is limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Otology & Neurotology · 2011 · 116 citations
Exclusive Endoscopic Ear Surgery for Acquired Cholesteatoma
AbstractOBJECTIVE: To present preliminary results in transmeatal exclusive endoscopic ear surgery. STUDY DESIGN: Retrospective. INTERVENTION: Rigid endoscopes were used for all procedures. A wide posterior tympanomeatal flap was elevated transmeatally, and the scutum was removed with a bone curette or was drilled until visualization of cholesteatoma extension and the mastoid antrum. The malleus and incus were removed when they were involved in the cholesteatoma or restricted access to it. When present, the stapes was left intact. Endoscopic accessibility was defined by no extension of the cholesteatoma beyond the level of the lateral semicircular canal. Scutumplasty was by with tragal cartilage, and tympanic membrane defects were reconstructed with the palisade technique and perichondrium. RESULTS: Thirty patients, aged 9 to 75 years, underwent the exclusive endoscopic transmeatal cholesteatoma eradication between July 2008 and May 2010. There were no incidents of iatrogenic injuries to the facial nerve or ossicles. Closure of the tympanic membrane and good hygienic status (water tolerance and absence of inflammation) were achieved in all operated ears. Two patients had significant postoperative worsening of their sensorineural hearing loss: the cholesteatoma of one of them involved all 3 ossicles and oval window and the other patient experienced postoperative labyrinthitis. There was no residual disease in 18 patients who were followed for more than 1 year, and the non-echo-planar base diffusion-weighted sequence magnetic resonance imaging was negative in 3 patients. CONCLUSION: Our preliminary results indicate that the minimally invasive endoscopic ear surgery allowed complete eradication of cholesteatoma from the middle ear and its extensions, with minimal morbidity and good functional results.
The middle ear cholesteatoma: definition, classification and etiopathogenesis issues (brief literature review). Part I
AbstractThis article provides a brief literature review of national and foreign authors’ works, presenting a brief historical sketch of the study of the middle ear cholesteatoma. The authors present cholesteatoma definition from the viewpoint of V. F. Undrits, L. T. Levin, V. T. Palchun, I. Friedmann, H. Schuknecht and other domestic and foreign authors. The article describes the modern concepts of its macroscopic and microscopic structure, giving coverage to the currently existing classifications. The authors consider the theories of the etiology and pathogenesis of congenital and acquired middle ear cholesteatoma.
[Advances in research on apoptosis in the pathogenesis of acquired middle ear cholesteatoma].
AbstractSquamous epithelial hyperplasia, cell apoptosis and bone destruction were thought to be three key mechanisms in the pathogenesis of middle ear cholesteatoma. At present, the research on the pathogenesis of middle ear cholesteatoma mainly focuses on these three major pathological events. Studies have shown that various apoptosis-related genes and regulatory factors are associated with the development of cholesteatoma.
Laryngo-Rhino-Otologie · 2019 · 0 citations · open access
Cholesteatoma in Transition
AbstractCholesteatoma is a destructing process of the middle ear due to non-self-limiting chronic proliferative inflammation. Possible consequences include destruction of bony structures with hearing loss, vestibular dysfunction, facial nerve paralysis and intracranial complications. The therapy of choice is surgical. So far, little is known for the etiopathogenesis of cholesteatoma. New studies focus on the innate immune system and the microbiome.
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.
