DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for obstructive sleep apnea — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleObstructive sleep apnea maps to a 35-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
approvedClozapineApproved drug
Structures already discussed alongside obstructive sleep apnea in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Clozapine-bound H4R/Gi complex — Clozapine has a real, experimentally solved structure in complex with this target (PDB 8JXV, 3.21 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet vbudrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8JXV · 3.21 Å · ligand Clozapine (VBU). Experimental structure, not a prediction.
What the evidence adds up to
A genome-wide association study of up to 12,558 Hispanic/Latino Americans from three cohorts identified the first genome-level significant findings for obstructive sleep apnea-related physiologic traits, including the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration. Multiple loci overlapped genes in inflammatory, hypoxia signalling, and sleep pathways, and secondary sex-stratified analyses identified one significant and several suggestive associations. No drug intervention was tested in this genetic study.
A 2006 randomised controlled trial in patients with congestive heart failure and obstructive sleep apnea (respiratory disturbance index greater than 15 per hour) tested acetazolamide or placebo taken one hour before bedtime for six nights. Patients receiving acetazolamide showed decreased central sleep apnea, improved oxygenation, and improved subjective perception of sleep quality. The authors noted that questions persist over long-term use of acetazolamide and the development of tolerance. The sample size was not given in the abstract.
A 2018 pilot study protocol estimated that obstructive sleep apnea syndrome may be present in 30 percent of clozapine-treated patients with schizophrenia spectrum disorder, based on the drug being an independent risk factor. The study planned to screen 30 to 50 stable outpatients using the Epworth Sleepiness Scale and STOP-Bang questionnaire, followed by ambulatory polysomnography if high risk was indicated. No results had been submitted at the time of the poster; results were to be presented in April 2018. A 2009 review stated that obstructive sleep apnea is underdiagnosed and that treatment is effective in improving quality of life and reducing morbidity, but did not test any drug.
What is still missing: no adequately powered randomised trial of acetazolamide for obstructive sleep apnea with long-term follow-up exists; the genetic findings have not been translated into a therapeutic target; the clozapine-OSA prevalence pilot has not reported results; no drug has been shown to modify the disease in a large, placebo-controlled trial with objective sleep endpoints.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Respiratory and Critical Care Medicine · 2016 · 137 citations · open access
Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans
AbstractRATIONALE: Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability. OBJECTIVES: To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts. METHODS: Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration. MEASUREMENTS AND MAIN RESULTS: ). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility. CONCLUSIONS: These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.
Journal of Cardiopulmonary Rehabilitation and Prevention · 2009 · 25 citations
Clinical Manifestations and Consequences of Obstructive Sleep Apnea
AbstractIn Brief Obstructive sleep apnea is a common respiratory disorder that is underdiagnosed and associated with a variety of adverse health and safety consequences. Treatment is effective in improving quality of life and reducing morbidity. This underscores the importance of considering the diagnosis in suitable patients, verifying the diagnosis, and initiating prompt, effective therapy. In this review, the risk factors, symptoms and signs, diagnosis, clinical consequences, and treatment of obstructive sleep apnea are discussed. Obstructive sleep apnea (OSA) is a common respiratory disorder that is underdiagnosed and associated with a variety of adverse health and safety consequences. In this review, the risk factors, symptoms and signs, diagnosis, clinical consequences, and treatment of OSA are discussed.
Schizophrenia Bulletin · 2018 · 0 citations · open access
F94. A PREVALENCE PILOT STUDY FOR OBSTRUCTIVE SLEEP APNEA SYNDROME IN CLOZAPINE USERS
AbstractObstructive Sleep Apnea Syndrome (OSAS) is a frequent and common disorder. Estimated 50.000 persons in the Netherlands suffer from this disorder. Clozapine is known for its efficacy in treatment resistant schizophrenia. Frequent side effects of clozapine are weight gain, fatigue, sleepiness and metabolic syndrome. Similar symptoms occur in the course a OSAS. The Dutch pharmacovigilance centre LAREB (LAREB 2012) proposed an association between OSAS and clozapine usage, independent of confounding factors as obesity, smoking and glucose intolerance. Although clozapine is much used in the treatment of schizophrenia, OSAS prevalence studies in the clozapine treatment group are scarce. Research is needed to elucidate the relationship between clozapine use and OSAS. Identifying OSAS and treatment with continuous positive airway pressure (CPAP) could possibly (Galletly te al, 2016), through reduction in cardiovascular risk factors, have a favorable effect on mortality and possibly have a positive effect on daytime sleepiness, fatigue and daytime functioning. Primary goal of this study is discovering the prevalence of OSAS in clozapine using schizophrenic spectrum disorder patients. The secondary goal is discovering how willing schizophrenic spectrum disorder patient are in undergoing a polysomnography. Many patients with schizophrenia spectrum disorder have multiple OSAS risk factors: obesity, presence of metabolic syndrome, frequent usage of benzodiazepines, male sex, older age. OSAS prevalence is estimated to be much higher than in the general population because of these risk factors. Atypical antipsychotics are an independent risk factor for the development of OSAS. Polysomnographically diagnosed OSAS will even be higher in the clozapine treatment group estimated to be present in 30% percent of the patients. Research design: prospective observational and cross-sectional study in a group of stable adult patients with DSM IV schizophrenia spectrum disorder treated with clozapine in an outpatient community mental health service. Estimated study group consists of 30–50 patients. Exclusion criteria: unwillingness to undergo a polysomnography, inability to give informed consent, insufficient understanding of the Dutch language, severe cardiac failure, a history a cerebrovascular accidents and alcohol abuse. screening on the presence of OSAS symptoms and risk factors associated with OSAS through: Epworth Sleepiness Scale for daytime sleepiness (Johns, 1991), STOP-BANG Questionaire ((SBQ: Chung 2012) when there is a high risk for OSAS followed by an ambulatory polysomnography including heart rate/ECG, respiratory measures with nasal flow canule and thermistor flow inductive respiratory movements, oximetry, and snoaring noises through sensory measurements (AASAM, 2009). OSAS is considered to be present in the presence of daytime sleepiness and if the Apnea Hypopnea Index (AHI) is larger than 5.0 obstructive or mixed type respiratory events per hour (AASM, 2009: Berry et. al, 2015: NVALT & CBO, 2009). Statistical analysis: polysomnography: descriptive and univariate analysis. Presence of OSAS will be dichomotized (1 =OSAS present; 0 = OSAS absent) Summation of the amount of positive results will be presented as percentage of the total study population. Chi- squared test for considering of the height of the results on the ESS test and the STOP-Bang test and the prevalence of OSAS. Statistical significance: p < 0.05. Prevalence: percentage of patients in the clozapine treatment group with OSAS. No results at the moment of poster submission. In April 2018 results will be presented. Will be presented in April 2018.
Indian Journal of Sleep Medicine · 2006 · 0 citations · open access
Clinical Research Update Corner
AbstractResearchers from Cincinnati, Ohio found that acetazolamide significantly improved Central sleep apnea and related daytime symptoms in patients with congestive heart failure.In this randomized controlled trial, patients with congestive heart failure and Obstructive Sleep apnea (RDI>15/hr) received acetazolamide or placebo, taken one hour before bedtime for six nights.Patient's receiving Acetazolamide showed decreased CSA, improved oxygenation and subjective perception of sleep quality.However questions persist over long term use of acetazolamide and development of tolerance.
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.
