DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for allergic respiratory disease — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAllergic respiratory disease maps to a 1-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 allergic respiratory disease 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
histamine receptor H1 (HRH1) — HRH1 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 hsmdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8YN2 · 2.66 Å · ligand HISTAMINE (HSM). Experimental structure, not a prediction.
What the evidence adds up to
A 2014 review of genome-wide association studies in allergic rhinitis, atopic dermatitis and allergic asthma found that susceptibility genes have been identified with confidence, including genes involved in both adaptive and innate immune mechanisms and multiple genes involved in epithelial function and secretion. The review noted that concordance and discordance between genetic factors driving IgE levels and disease states such as asthma support evidence for heterogeneity in these diseases. A 2021 review focused on the CCR3 gene as a major research target in respiratory allergic diseases, stating that related inflammatory cells are the main cells responding to the downstream cascade triggered by CCR3 activation, and that these cells directly or indirectly cause allergic inflammation.
A 2019 prospective observational study in France treated 39 adults with severe asthma and antibody deficiency for one year with either azithromycin (250 mg every other day, 14 patients) or subcutaneous immunoglobulins (0.4-0.6 g/kg/month weekly, 25 patients). Before treatment, all patients had an Asthma Control Questionnaire score above 1.5 (mean 2.71) despite GINA step 4 or 5 treatment, and had a high exacerbation rate requiring oral corticosteroids or rescue antibiotics (about 7.2 per patient per year). One year after treatment initiation, mean FEV1 increased by 0.18 litres, mean ACQ-7 score fell to 1.26, and the exacerbation rate dropped to 1.63 per patient per year. The authors concluded that treatment of antibody deficiency dramatically improved asthma outcomes.
A 2024 Danish register-based cohort study examined the effectiveness of pollen allergen immunotherapy over 18 years in 7760 treated patients with allergic rhinitis matched to 15,520 non-treated individuals. The odds ratio for using an anti-allergic nasal inhaler during the pollen season was reduced 0-2 years after baseline (OR 0.84) and 3-5 years after baseline (OR 0.88), but was close to unity or higher thereafter (6-9 years OR 1.03; 10-18 years OR 1.18). Post hoc analyses suggested more consistent effectiveness among patients with persistent allergic rhinitis who had used a nasal inhaler in the latest pollen season, with odds ratios of 0.76 at 0-2 years, 0.86 at 3-5 years, 0.94 at 6-9 years, and 0.94 at 10-18 years. A 2022 review stated that first-line pharmacologic options for allergic rhinitis include non-sedating second-generation oral H1-antihistamines and intranasal corticosteroids, and that allergen immunotherapy is a possible treatment for moderate-to-severe disease uncontrolled by first-line therapies.
What is still missing are large randomised controlled trials of immunoglobulin replacement and azithromycin specifically in severe asthma with antibody deficiency, replication of the Danish AIT findings in other healthcare systems, and any clinical application of the CCR3 gene target. The genetic studies have not yet translated into new treatments, and the long-term effectiveness data for AIT beyond five years remain disappointing in the general population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Genetic risk factors for the development of allergic disease identified by genome‐wide association
AbstractAn increasing proportion of the worldwide population is affected by allergic diseases such as allergic rhinitis (AR), atopic dermatitis (AD) and allergic asthma and improved treatment options are needed particularly for severe, refractory disease. Allergic diseases are complex and development involves both environmental and genetic factors. Although the existence of a genetic component for allergy was first described almost 100 years ago, progress in gene identification has been hindered by lack of high throughput technologies to investigate genetic variation in large numbers of subjects. The development of Genome-Wide Association Studies (GWAS), a hypothesis-free method of interrogating large numbers of common variants spanning the entire genome in disease and non-disease subjects has revolutionised our understanding of the genetics of allergic disease. Susceptibility genes for asthma, AR and AD have now been identified with confidence, suggesting there are common and distinct genetic loci associated with these diseases, providing novel insights into potential disease pathways and mechanisms. Genes involved in both adaptive and innate immune mechanisms have been identified, notably including multiple genes involved in epithelial function/secretion, suggesting that the airway epithelium may be particularly important in asthma. Interestingly, concordance/discordance between the genetic factors driving allergic traits such as IgE levels and disease states such as asthma have further supported the accumulating evidence for heterogeneity in these diseases. While GWAS have been useful and continue to identify novel genes for allergic diseases through increased sample sizes and phenotype refinement, future approaches will integrate analyses of rare variants, epigenetic mechanisms and eQTL approaches, leading to greater insight into the genetic basis of these diseases. Gene identification will improve our understanding of disease mechanisms and generate potential therapeutic opportunities.
Journal of Intensive Care Medicine · 2008 · 51 citations
Acute Respiratory Distress Syndrome From Chlorine Inhalation During a Swimming Pool Accident: A Case Report and Review of the Literature
AbstractChlorine inhalation can result in significant morbidity and mortality. The most common clinical ramification is mucosal irritation. Rarely, depending upon the degree of exposure, patients can develop acute respiratory distress syndrome. Management is usually supportive with an unproven role for inhaled or systemic corticosteroids. A case of a young woman who developed respiratory failure secondary to acute respiratory distress syndrome from accidental exposure to chlorine fumes at a community swimming pool is described. The patient suffered a prolonged hospitalization with the need for mechanical ventilation. Despite limited data to support the decision, the patient was started on treatment with corticosteroids. She recovered completely from her illness and was discharged home without supplemental oxygen. A concise discussion of chlorine inhalation injury and a literature review on the utility of inhaled and/or systemic corticosteroids for this clinical entity is presented.
Allergology International · 2019 · 15 citations · open access
Efficacy of immunoglobulin replacement therapy and azithromycin in severe asthma with antibody deficiency
AbstractBACKGROUND: Although antibody deficiency (AD) is a well-known cause of recurrent respiratory infections, there are few data on its impact in adults with asthma. The objective of the present study was to assess outcomes in adults with severe asthma and AD after treatment with either azithromycin or subcutaneous immunoglobulins (SCIg). METHODS: We performed a 5-year, prospective, observational, two-centre study of adults with severe asthma and AD in France. Bronchiectasis was ruled out by high-resolution computed tomography. Patients were treated for one year with either azithromycin (250 mg every other day) or SCIg (0.4-0.6 g/kg/months, weekly). All patients were evaluated for exacerbations, asthma control and lung function at baseline and then one year after treatment initiation. RESULTS: Thirty-nine patients with severe asthma were included in the study: 14 had been treated with azithromycin and 25 had been treated with SCIg. Before the initiation of treatment for AD, all patients had an Asthma Control Questionnaire (ACQ-7) score > 1.5 (mean ± SD: 2.71 ± 0.53) despite treatment at GINA step 4 or 5, and had a high exacerbation rate requiring oral corticosteroids and/or rescue antibiotics (∼7.2 ± 2.1/patient/year). One year after treatment initiation, we observed a significantly higher FEV1 (mean: 0.18 ± 0.22 L) and ACQ-7 score (1.26 ± 0.68), and a significantly lower exacerbation rate (1.63 ± 1.24/patient/year). CONCLUSIONS: Treatment of AD dramatically improved asthma outcomes - suggesting that adults with severe asthma and recurrent respiratory infections should be screened and (if appropriate) treated for AD.
The effectiveness of pollen allergen immunotherapy on allergic rhinitis over 18 years: A national cohort study in Denmark
AbstractBACKGROUND: Because long-term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well-described, we studied effectiveness over 18 years in Denmark. METHODS: A register-based cohort study using data on filled prescriptions, 1995-2016, Denmark. In a cohort of 1.1 million intranasal corticosteroid inhaler users (proxy for AR), we matched users treated with grass, birch or mugwort AIT 1:2 with non-treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti-allergic nasal inhaler during the pollen season in the treated versus non-treated group by years since baseline. RESULTS: Among 7760 AR patients treated with pollen AIT, the OR of using nasal inhaler 0-5 years after baseline was reduced when compared with 15,520 non-treated AR individuals (0-2 years, OR 0.84 (0.81-0.88); 3-5 years, OR 0.88 (0.84-0.92)), but was close to unity or higher thereafter (6-9 years, OR 1.03 (0.97-1.08); 10-18 years, OR 1.18 (1.11-1.26)). In post hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use, and in patients using nasal inhaler in the latest pollen season (0-2 years, OR 0.76 (0.72-0.79); 3-5 years OR 0.86 (0.81-0.93); 6-9 years, OR 0.94 (0.87-1.02); 10-18 years, OR 0.94 (0.86-1.04)) as opposed to no such use. CONCLUSIONS: Patients treated with pollen AIT in routine care to a higher degree stopped using anti-allergic nasal inhaler 0-5 years after starting the standard 3 years of therapy, and not beyond 5 years. Post hoc analyses suggested effectiveness was more consistent among patients with persistent AR.
[Effect of CCR3 gene on related inflammatory cells in respiratory allergic diseases].
AbstractRespiratory allergic disease mainly include asthma and allergic rhinitis.According to their extremely similarpathogenesis and inflammatory pathological changes,asthma and allergic rhinitis,are regarded as the concept of "one airway, one disease". In recent years, The research on the target of allergens in the pathogenesis mechanism is more in-depth, and the CCR3 gene is a major research target. The study found that the CCR3 gene is an important target gene for the development of respiratory allergic diseases such as allergic rhinitis and asthma. The related inflammatory cells are the main cells responding for the downstream cascade triggered by CCR3 activation, which directly or indirectly cause allergic inflammation through itself or its secretions.Therefore, researches on the roles of CCR3 gene and its related inflammatory cells become hot topics in the clinical treatment of respiratory allergic diseases. This paper reviews the current research progress of respiratory allergic diseases on the basis of intensive literature.
Canadian allergy & immunology today. · 2022 · 0 citations · open access
Future of Allergic Rhinitis Management
AbstractAllergic rhinitis (AR) is an inflammatory condition affecting the nasal mucosa mediated byimmunoglobulin-E (IgE). It impacts an estimated 25% of Canadians, of whom most report inadequatesymptom control despite treatment as well as highrates of asthma comorbidity. First line pharmacologic options include non-sedating, 2nd generation oral H1-antihistamine (OAH) and/or intranasal corticosteroid (INCS) therapeutic agents. Allergen immunotherapy (AIT) is a possible treatment option for moderate-to-severe disease which is uncontrolled with the use of first-line therapies or for those patients wishing to avoid pharmacologic intervention. However, patient education, engagement, and empowerment are central to optimal clinica outcomes. This supplement summarizes the literature to present the future of AR 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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