DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for non-suppurative otitis media — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNon-suppurative otitis media maps to a 7-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 non-suppurative otitis media 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
fragile histidine triad diadenosine triphosphatase (FHIT) — FHIT 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 frudrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1FIT · 1.85 Å · ligand beta-D-fructofuranose (FRU). Experimental structure, not a prediction.
What the evidence adds up to
In a mouse model of acute otitis media induced by non-typeable Haemophilus influenzae, about 8% of sampled transcripts defined the gene expression signature of the infection across time. Network analysis identified sets of genes involved in innate immune activation, negative regulation of immune response, changes in epithelial and stromal cell markers, and recruitment of neutrophils and macrophages. Positive and negative regulation of inflammation occurred with highly similar kinetics, underscoring the importance of anti-inflammatory responses in controlling pathogenesis. The authors concluded that dysregulated immune defence and inflammatory responses may contribute to recurrent or chronic otitis in children.
Twin and triplet studies have confirmed a strong genetic component to otitis media susceptibility. Pilot studies linked IFN-gamma polymorphisms, allotypes of leukocyte FcgammaR receptors, and certain surfactant gene haplotypes to susceptibility. Mucin and cathepsin protease genes were shown to be modulated during infection and potentially polymorphic. By 2017, many genes relevant to otitis media had been identified through mutant animal models and clinical studies, involving multiple signalling pathways in predisposition of the middle ear mucosa. The molecular understanding of disease progression has advanced rapidly, with roles of inflammation, mucins, and cell signalling mechanisms elucidated.
Bacterial biofilms may account for persistence of middle ear disease. Evidence from reviews indicates that medical and surgical therapy are of limited utility in managing acute and recurrent acute otitis media, and antibiotics and steroids are of limited value in treating chronic middle ear effusion. Delayed management of effusion may not adversely affect development in children. Vaccination for pneumococcus may alter the serotypes responsible for otitis media, and vaccine candidates for other middle ear pathogens are under investigation.
What is still missing is the translation of these genetic and molecular findings into treatments that work in children. No drug has been shown in these abstracts to alter the course of non-suppurative otitis media. The identified gene networks and signalling pathways have not yet been targeted in a clinical trial. Patient stratification by genetic susceptibility remains a research concept, not a clinical tool. Money for trials, a trial design that can measure meaningful outcomes in chronic effusion, and a way to identify which children might benefit from a molecular intervention are all absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BMC Genomics · 2015 · 54 citations · open access
The transcriptome of a complete episode of acute otitis media
AbstractBACKGROUND: Otitis media is the most common disease of childhood, and represents an important health challenge to the 10-15% of children who experience chronic/recurrent middle ear infections. The middle ear undergoes extensive modifications during otitis media, potentially involving changes in the expression of many genes. Expression profiling offers an opportunity to discover novel genes and pathways involved in this common childhood disease. The middle ears of 320 WBxB6 F1 hybrid mice were inoculated with non-typeable Haemophilus influenzae (NTHi) or PBS (sham control). Two independent samples were generated for each time point and condition, from initiation of infection to resolution. RNA was profiled on Affymetrix mouse 430 2.0 whole-genome microarrays. RESULTS: Approximately 8% of the sampled transcripts defined the signature of acute NTHi-induced otitis media across time. Hierarchical clustering of signal intensities revealed several temporal gene clusters. Network and pathway enrichment analysis of these clusters identified sets of genes involved in activation of the innate immune response, negative regulation of immune response, changes in epithelial and stromal cell markers, and the recruitment/function of neutrophils and macrophages. We also identified key transcriptional regulators related to events in otitis media, which likely determine the expression of these gene clusters. A list of otitis media susceptibility genes, derived from genome-wide association and candidate gene studies, was significantly enriched during the early induction phase and the middle re-modeling phase of otitis but not in the resolution phase. Our results further indicate that positive versus negative regulation of inflammatory processes occur with highly similar kinetics during otitis media, underscoring the importance of anti-inflammatory responses in controlling pathogenesis. CONCLUSIONS: The results characterize the global gene response during otitis media and identify key signaling and transcription factor networks that control the defense of the middle ear against infection. These networks deserve further attention, as dysregulated immune defense and inflammatory responses may contribute to recurrent or chronic otitis in children.
Current Opinion in Allergy and Clinical Immunology · 2005 · 41 citations
Genetic susceptibility to otitis media
AbstractPURPOSE OF REVIEW: Otitis media is a disease that is prevalent in the pediatric population, and recent twin and triplet studies have confirmed that there is a strong genetic component to susceptibility. Here, we summarize the status of current efforts to identify the specific genes underlying otitis media susceptibility and presentation. RECENT FINDINGS: Recent studies have focused on identifying candidate genes. For example, IFN-gamma polymorphisms, allotypes of the leukocyte IgG (FcgammaR) receptors and certain haplotypes of surfactant genes were linked in pilot studies to otitis media susceptibility. The pattern of gene expression during an episode of otitis media is also being elucidated with the overall goal of providing clues as to which of these modulated genes are polymorphic and thus potentially capable of affecting otitis media susceptibility. Mucin and cathepsin protease genes were shown to exhibit these characteristics. SUMMARY: In addition to the simple searches for linkages between known genes and otitis media, work is progressing within the context of genome-wide linkage studies. These efforts promise to answer some of the many questions remaining in otitis media susceptibility and pathogenesis.
Current Opinion in Otolaryngology & Head & Neck Surgery · 2003 · 28 citations
Otitis media: concepts and controversies
AbstractPURPOSE OF REVIEW: Otitis media is the most common bacterial infection among children, accounting for as many as 30 million office visits annually. Proper treatment has become critical as offending pathogens become increasingly resistant to antibiotics and the cost of managing the disorder has exceeded 3 billion dollars per year. However, data suggest that many practitioners still struggle with the diagnosis of otitis media and often recommend medical and surgical intervention inappropriately. This article presents recent advances in the otitis media literature and an evidence-based approach to its management. RECENT FINDINGS: Recent investigations have resulted in the following findings: (1) bacterial biofilms may account for the persistence of middle ear disease; (2) there is increasing evidence that heredity and reflux are risk factors for otitis media; (3) primary care providers may be receiving poor otitis media training, leading to inadequate diagnostic skills; (4) medical and surgical therapy are of limited utility in the management of acute and recurrent acute otitis media; (5) antibiotics and steroids are of limited value in the treatment of chronic middle ear effusion; (6) delayed management of effusion may not adversely affect development in children; (7) vaccination for pneumococcus may alter the serotypes responsible for otitis media; and (8) vaccine candidates for other middle ear pathogens are under investigation. SUMMARY: Management of otitis media is constantly evolving, based on research from a variety of medical subspecialties. It is incumbent on the otolaryngologist and primary care providers treating otitis media to keep pace with and synthesize these findings into a rational approach to treatment.
Current Opinion in Otolaryngology & Head & Neck Surgery · 2008 · 7 citations · open access
Bench and bedside advances in otitis media
AbstractPURPOSE OF REVIEW: Otitis media continues to be an important pediatric illness and requires significant expenditures in management and treatment. Despite its prevalence and importance, clinicians often have significant knowledge deficits regarding the most up-to-date research or clinical thinking regarding this disease. The present review aims to discuss recent and important publications related to otitis media and present an analysis of some of these findings. RECENT FINDINGS: Major basic science and clinical themes related to otitis media are discussed and include the importance of biofilms in otitis media pathogenesis, the evidence that otitis media with effusion impacts development, the impact of otitis media treatment on quality of life, risk factors associated with otitis media and current concepts with respect to vaccine strategies and otitis media. SUMMARY: Important basic and clinical research in the field of otitis media continues to clarify our understanding of the pathogenesis of this disease and drive new paradigms in treatment and clinical management.
Panel 3: Genetics and Precision Medicine of Otitis Media
AbstractObjective The objective is to perform a comprehensive review of the literature up to 2015 on the genetics and precision medicine relevant to otitis media. Data Sources PubMed database of the National Library of Medicine. Review Methods Two subpanels were formed comprising experts in the genetics and precision medicine of otitis media. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a merged draft was created. The entire panel met at the 18th International Symposium on Recent Advances in Otitis Media in June 2015 and discussed the review and refined the content. A final draft was made, circulated, and approved by the panel members. Conclusion Many genes relevant to otitis media have been identified in the last 4 years in advancing our knowledge regarding the predisposition of the middle ear mucosa to commensals and pathogens. Advances include mutant animal models and clinical studies. Many signaling pathways are involved in the predisposition of otitis media. Implications for Practice New knowledge on the genetic background relevant to otitis media forms a basis of novel potential interventions, including potential new ways to treat otitis media.
Archives of Otolaryngology - Head and Neck Surgery · 1937 · 7 citations
A TREATMENT OF CHRONIC PURULENT OTITIS MEDIA
AbstractBy using common sense and ordinary judgment one must conclude that the percentage of cases of chronic purulent otitis media in the population is much less now than it was two or three decades ago. There is room for improvement. Otologists agree that the chronically suppurating ear should be kept clean and little has been added to this one principle in a decade or two or three. During this time radical mastoidectomy, zinc ionization, treatment with silver nitrate and other procedures were at different times hailed as the answer. Hett, Wells and Levick<sup>1</sup>reported 75 per cent of cures with zinc ionization. Perhaps nearly as great a percentage could be obtained by keeping these same ears clean with dry cotton followed by the insufflation of boric acid powder. Lederman<sup>2</sup>laid great stress on thorough cleansing of the ear before iodine powder is used. To my mind, cleansing is the most
Panel 8: Report on Recent Advances in Molecular and Cellular Biochemistry
AbstractObjectives To update the medical literature on recent cellular and molecular advances in otitis media disease models with a principal focus on developments in the past 5 years. We also aim to explain recent translational advances in cellular and molecular biology that have influenced our understanding and management of otitis media. Data Sources PubMed-indexed peer-reviewed articles. Review Methods A comprehensive review of the literature was conducted with the term otitis media and the following search terms: molecular biology, cell biology, innate immunity, oxidative stress, mucins, molecular diagnostics. Included articles were published in the English language from January 1, 2010, to July 31, 2015. Implications for Practice The molecular understanding of otitis media disease progression has rapidly advanced over the last 5 years. The roles of inflammation, mucins, and cell signaling mechanisms have been elucidated and defined. Advances in the field provide a plethora of opportunities for innovative molecular targeting in the development of novel therapeutic strategies for otitis media.
Current Opinion in Otolaryngology & Head & Neck Surgery · 1994 · 0 citations
Otitis media
AbstractOtitis media as a clinical entity has received significant press recently both in the lay and professional literature. Despite recent debate regarding management protocols, significant basic and clinical research continues in an attempt to limit the untoward effects of this very common pathologic process. This review directs attention to newer concepts regarding both the pathobiology of otitis media and the pharmacotherapy available for management.
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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