DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for hypersensitivity pneumonitis — 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 moduleHypersensitivity pneumonitis 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 hypersensitivity pneumonitis 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
nuclear receptor subfamily 3 group C member 1 (NR3C1) — NR3C1 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7KW7 · 3.57 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
A 1992 case study of a 51-year-old man with chronic bronchitis found that reexposure to minocycline, but not to amoxicillin, produced an interstitial pneumonitis within one month. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis composed of CD8+ and CD4+ cells. Two CD8+ subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed, and CD8+ CD57+ suppressor T cells that predominated 11 days after withdrawal. In-vitro assays showed lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. The authors concluded these results supported a central role for T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.
A 2004 review stated that hypersensitivity pneumonitis is a group of immunologically mediated diseases caused by an abnormal response to a wide variety of inhaled antigens. It noted that over the previous three years new antigens had been identified and that the role of inflammatory cells and mediators was better understood, with promoting and protective factors suggested. The review summarised that most mechanisms involved in the pathogenesis remained incompletely understood.
A 2010 review noted that the literature continued to bring forth new conditions that can cause hypersensitivity pneumonitis. It highlighted new findings in diagnosis, histopathology, insight into potential outcomes, and understanding of immune mechanisms that could lead to new treatments. It described hypersensitivity pneumonitis as a worldwide orphan disease.
A 2015 review stated that hypersensitivity pneumonitis is a complex syndrome combining inflammation and fibrosis in both airways and lung parenchyma. It noted that the main diagnostic issue is not to miss the entity because the clinical presentation is extremely variable, even regarding the nature of the causal antigen. The review stated that crucial in treatment is antigen avoidance, often in combination with immunosuppressive agents, but that the biggest challenge is treatment of chronic forms, which do not always respond to immunosuppressive agents. It concluded that diagnosis and treatment remain a real challenge. What is still missing is a proper diagnostic framework that accounts for the variable presentation, and more efficacious treatments for the chronic fibrotic form, which current immunosuppression does not reliably address.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractOBJECTIVE: To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. DESIGN: Case study. SETTING: Intensive care unit of a referral hospital. PATIENT: A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. INTERVENTION: Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. MEASUREMENTS: Immunologic analysis of the phenotype and function of alveolar lymphocytes. RESULTS: Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. CONCLUSION: These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.
Current Opinion in Allergy and Clinical Immunology · 2004 · 64 citations
Pathogenesis of hypersensitivity pneumonitis
AbstractPURPOSE OF REVIEW: Hypersensitivity pneumonitis is a group of immunologically mediated diseases caused by an abnormal response to a wide variety of inhaled antigens. Its pathogenesis is complex and involves many immunological concepts. This review discusses recent advances in our understanding of the pathogenesis of hypersensitivity pneumonitis. RECENT FINDINGS: Over the last 3 years, several studies on the pathogenesis of hypersensitivity pneumonitis have been published. New antigens have been identified. We now have a better understanding of the role of inflammatory cells and mediators, and promoting and protective factors have been suggested. SUMMARY: Most of the mechanisms involved in the pathogenesis of hypersensitivity pneumonitis remain incompletely understood. Current and future findings will not only help our understanding of the disease and its prevention, but also improve its treatment.
Current Opinion in Allergy and Clinical Immunology · 2010 · 37 citations
Hypersensitivity pneumonitis
AbstractPURPOSE OF REVIEW: To bring readers up to date on recent reports, both clinical and basic understanding, on hypersensitivity pneumonitis. RECENT FINDINGS: Although many antigens and environmental settings have already been described as sources of this hyperimmune pulmonary disease, the literature continues to bring forth other conditions that can cause hypersensitivity pneumonitis. We also highlight new findings in the diagnosis of hypersensitivity pneumonitis, its histopathology, insight into its potential outcomes, and understanding of its immune mechanisms that could lead to new treatments. SUMMARY: The review will help clinicians in their diagnostic approach to hypersensitivity pneumonitis and lead them to look for other potential sources of the disease. The findings described will help guide further research on the pathophysiology and seek new treatments for this worldwide orphan disease.
Current Opinion in Pulmonary Medicine · 2015 · 25 citations
Pitfalls in diagnosis and management of hypersensitivity pneumonitis
AbstractPURPOSE OF REVIEW: Hypersensitivity pneumonitis is a complex syndrome characterized by a combination of inflammation and fibrosis located in both the airways and the lung parenchyma. Both diagnosis and treatment are a real challenge for physicians. This review will focus on recent developments in this emerging field; furthermore, we will emphasize major gaps in the current knowledge, to stimulate further research in this field. RECENT FINDINGS: The main diagnostic issue is not to miss the entity as the clinical presentation is extremely variable even as the nature of the causal antigen. This article provides an overview of current ways to uncover possible causes of hypersensitivity pneumonitis. A problem of another kind is treatment of this disorder. Crucial in treatment is antigen avoidance, often in combination with immunosuppressive agents. The treatment of acute forms is rather straightforward, but the biggest endeavour, however, is treatment of chronic forms of hypersensitivity pneumonitis, which not always respond to immunosuppressive agents. Therefore, new initiatives should be taken in order to help clinicians in making a proper diagnosis and develop more efficacious treatment especially for patients suffering from chronic hypersensitivity pneumonitis. SUMMARY: Diagnosis and treatment of hypersensitivity pneumonitis remain a real challenge; this article provides an overview of our current understanding and points out new opportunities for further research.
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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