DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for bronchiectasis — screening already-approved drugs against its 36-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBronchiectasis maps to a 36-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 bronchiectasis 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
phosphodiesterase 4D (PDE4D) — PDE4D 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 difluoromethoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5WH6 · 1.6 Å · ligand 1-[4-(difluoromethoxy)-3-{[(3S)-oxolan-3-yl]oxy}phenyl]-3-methylbutan-1-one (AKJ). Experimental structure, not a prediction.
What the evidence adds up to
A 2019 commentary on bronchiectasis trials states that no treatments have been approved by the US Food and Drug Administration or the European Medicines Agency for the condition, and that numerous recent clinical trials of investigational agents thought to hold great promise did not demonstrate a clinically or statistically significant benefit. The commentary attributes these disappointing results to the disease’s heterogeneity and the low quality of evidence underlying most current treatments. A 2018 review similarly notes that bronchiectasis is very heterogeneous and can be studied from a phenotypic standpoint to define its pathophysiological mechanisms, which may enable identification of patients suitable for inclusion in specific clinical trials of new drugs.
A 2002 surgical series of 166 patients who underwent pulmonary resection for bronchiectasis reported that symptoms were copious purulent sputum in 135 patients, foul-smelling sputum in 109, haemoptysis in 35, and cough in all. The indication for surgery was failure of medical therapy in 158 patients, massive haemoptysis in five, and lung abscess in three. Operative morbidity was 10.5% and mortality 1.7%. Among 148 patients with complete follow-up (mean 4.2 years), 111 were asymptomatic after surgery, symptoms improved in 31, and were unchanged or worse in six. The authors concluded that surgical treatment is more effective in patients with localised disease.
A 2018 update reports that two large bronchiectasis patient registries published initial demographic data in 2017, and that a consensus definition of exacerbation has been agreed. The same update notes that novel treatments, including repurposing of older therapies, have been published in 2016–2017, and that a new European guideline for management of adult bronchiectasis is now available. A 2018 review of pharmacotherapy options states that bronchiectasis is an increasingly common disease with significant impact on quality of life and morbidity.
What is still missing is a clear understanding of which patient subgroups might respond to specific treatments, given the repeated failure of large trials that treat bronchiectasis as a single disease. The 2019 commentary argues that the field needs to stop repeating the same trial designs and expecting different results. No drug repurposing candidate has yet shown efficacy in a phase 3 trial for bronchiectasis, and no drug is approved for the condition by US or European regulators. The necessary next steps include better patient stratification by endotype, funding for trials that account for disease heterogeneity, and a willingness to abandon agents that fail to show benefit in well-defined subgroups.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Cardio-Thoracic Surgery · 2002 · 87 citations · open access
Surgical treatment in bronchiectasis: analysis of 166 patients
AbstractBACKGROUND: Bronchiectasis is usually caused by pulmonary infections and bronchial obstruction. It is still a serious problem in developing countries as our country. We reviewed the morbidity and mortality rates and outcome of surgical treatment for bronchiectasis. PATIENTS AND METHODS: Between 1990 and 2000, 166 patients (92 female and 74 male patients) underwent pulmonary resection for bronchiectasis. The mean age was 34.1 years (range, 7-70 years). Mean duration of symptoms was 5.7 years. RESULTS: Symptoms were copious amount of purulent sputum in 135 patients, expectoration of foul-smelling sputum in 109, hemoptysis in 35 and cough in all patients. The indication for pulmonary resection was failure of medical therapy in 158 patients, massive hemoptysis in five and lung abscess in three. The disease was bilateral in six patients and mainly confined to the lower lobe in 127. One hundred and twenty patients had a lobectomy, 13 had a pneumonectomy, 21 had a segmentectomy and a combination of these approaches in 18. Operative morbidity and mortality were seen in 18 (10.5%) and in three (1.7%) patients, respectively. Follow-up was complete in 148 patients with a mean of 4.2 years. Overall, 111 patients were asymptomatic after surgical treatment, symptoms were improved in 31, and unchanged or worse in six. CONCLUSIONS: Surgical treatment of bronchiectasis is more effective in patient with localized disease. It is satisfactory with acceptable ratio of morbidity and mortality.
Cochrane Database of Systematic Reviews · 2000 · 34 citations · open access
Oral methylxanthines for bronchiectasis
AbstractBACKGROUND: Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the management of airflow limitation associated with asthma and COPD, where they are also purported to have anti-inflammatory properties. In theory they may be of use in bronchiectasis. OBJECTIVES: To determine the efficacy of methylxanthines in the treatment of bronchiectasis. SEARCH STRATEGY: The Cochrane Airways Group clinical trials register derived from MEDLINE,EMBASE and hand searches using the terms bronchiectasis, aminophylline, theophylline and methyl- xanthine SELECTION CRITERIA: Only randomised controlled trials were to be considered. DATA COLLECTION AND ANALYSIS: The results of the searches were reviewed by two authors. Searches yielded seven trials none of which met the inclusion criteria. MAIN RESULTS: No randomised controlled trials were identified. REVIEWER'S CONCLUSIONS: Further research is required to establish if the methylxanthines have a role in the treatment of bronchiectasis.
Current Opinion in Infectious Diseases · 2018 · 25 citations
Bronchiectasis update
AbstractPURPOSE OF REVIEW: Bronchiectasis, once thought to be an orphan disease, is being diagnosed with increased frequency in the United States and around the world. The present review aims to provide an update on recent publications on the diagnosis and management of bronchiectasis. RECENT FINDINGS: Two large bronchiectasis patient registries have published initial reports regarding demographics and other patient data in 2017. Updates on the microbiology, microbiome, and inflammation in patients with bronchiectasis are clarifying the complexities of airway infection in this disease. A consensus definition of 'exacerbation' in bronchiectasis has been agreed upon this year. Reports on novel treatments, including the repurposing of older therapies, have also been published in 2016-2017. A new European guideline for the management of adult bronchiectasis is also now available. SUMMARY: Bronchiectasis, a resurgent disease, is now being better defined with a rapidly expanding portfolio of demographic, clinical, and therapeutic research and publications.
Bronchiectasis insanity: Doing the same thing over and over again and expecting different results?
AbstractBronchiectasis is an increasingly common disease with a significant impact on quality of life and morbidity of affected patients. It is also a very heterogeneous disease with numerous different underlying etiologies and presentations. Most treatments for bronchiectasis are based on low-quality evidence; consequently, no treatments have been approved by the US Food and Drug Administration or the European Medicines Agency for the treatment of bronchiectasis. The last several years have seen numerous clinical trials in which the investigational agent, thought to hold great promise, did not demonstrate a clinically or statistically significant benefit. This commentary will review the likely reasons for these disappointing results and a potential approach that may have a greater likelihood of defining evidence-based treatment for bronchiectasis.
Expert Review of Respiratory Medicine · 2018 · 8 citations
Current and future pharmacotherapy options for non-cystic fibrosis bronchiectasis
AbstractINTRODUCTION: In recent years, there has been an increasing number of clinical trials investigating the effect of pharmacological treatments on patients with bronchiectasis. Areas covered: This review provides an overview of current drugs used in bronchiectasis patients as well as those that could make a future contribution to the management of this disease. Expert commentary: Bronchiectasis is a very heterogeneous disease, so it can be studied from a phenotypic standpoint and its pathophysiological mechanisms (endotypes) can be defined. This provides an interesting field of research as it enables the identification of patients suitable for inclusion in specific clinical trials on new drugs.
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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