DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for Coronary Vasospasm — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCoronary Vasospasm maps to a 5-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 coronary vasospasm 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 5A (PDE5A) — PDE5A 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 1-methyl-7-oxo-3-propyl-6,7-dihydro-1h-pyrazolo[4,3-d]pyrimidin-5-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3BJC · 2.0 Å · ligand 5-ethoxy-4-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-2-sulfonamide (WAN). Experimental structure, not a prediction.
What the evidence adds up to
Coronary vasospasm is recognised as a global disease, not limited to East Asia, and can cause significant symptoms, myocardial infarction, malignant arrhythmias, and sudden cardiac death. A 2010 review notes that understanding of interactions between inflammation, endothelium, and smooth muscle has progressed, but therapy still does not address the primary etiology. A 2012 report states that provocation studies for diagnosis are rarely performed due to procedural risks and the low incidence of disease, and that a subset of patients does not respond to conventional medical therapy, with little evidence to guide treatment.
A 2022 study of 75 patients with angina and no obstructive coronary artery disease who underwent a coronary function test found that those with acetylcholine-induced coronary vasospasm had a higher lipid index (819.85 vs 269.95, p=0.03) and a higher prevalence of vulnerable plaques (66% vs 38%, p=0.04) compared to those without spasm. Neovascularisation was also more common in the spasm group (37% vs 6%, p=0.02), and there was a trend toward more thin-cap fibroatheroma (20% vs 0%, p=0.06). The presence of vasospasm, regardless of phenotype, was associated with higher lipid burden and plaque vulnerability.
For refractory cases, a 2012 report describes successful treatment of focal vasospasm with coronary stent implantation, and notes that an implantable cardioverter defibrillator may be considered when vasospasm is complicated by lethal ventricular arrhythmias. A 2007 review also mentions the development of percutaneous coronary interventions in treatment. What remains missing is a therapy that addresses the underlying pathophysiology or primary etiology, as well as robust evidence from larger, stratified trials to guide management of patients who do not respond to conventional drugs.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
World Journal of Cardiology · 2010 · 17 citations · open access
Current advances in the understanding of coronary vasospasm
AbstractRecent years have witnessed progress in our understanding of coronary vasospasm (CVS). It is evident that this is not only an East Asian but also a global disease associated with significant symptoms and possible lethal sequelae for afflicted individuals. A correct diagnosis depends on the understanding of pathogenesis and symptomatology of CVS. With the correct diagnosis, we can manage CVS patients effectively and promptly, providing optimal patient safety. Advances in our understanding of interactions between inflammation, endothelium, and smooth muscle cells have led to substantial progress in understanding the pathogenesis of symptoms in CVS and have provided some insights into the basic etiology of this disorder in some patient subpopulations. We look forward to a time when therapy will address pathophysiology and perhaps, even the primary etiology.
EuroIntervention · 2022 · 13 citations · open access
Features of atherosclerosis in patients with angina and no obstructive coronary artery disease
AbstractBACKGROUND: An association between atherosclerosis and coronary vasospasm has previously been suggested. However, to date, no conclusive data on the whole spectrum of these disorders have been published. AIMS: This study aimed to define specific morphological features of atherosclerosis in patients with angina and no obstructive coronary artery disease (ANOCA) due to coronary vasospasm. METHODS: From February 2019 to January 2020, we enrolled 75 patients referred to our laboratory for a coronary function test (CFT) due to ANOCA and suspected coronary vasomotor dysfunction. The CFT consisted of an acetylcholine test and a physiology assessment with hyperaemic indexes using adenosine. Patients were divided into two groups according to the presence or absence of coronary vasospasm triggered by acetylcholine (ACH+ and ACH-, respectively). In addition, optical coherence tomography (OCT) was performed to assess the lipid index (LI), a surrogate for lipid area, and the prevalence of markers of plaque vulnerability. RESULTS: ACH+ patients had a higher LI than ACH- patients (LI: 819.85 [460.95-2489.03] vs 269.95 [243.50-878.05], respectively, p=0.03), and a higher prevalence of vulnerable plaques (66% vs 38%, p=0.04). Moreover, ACH+ patients showed a higher prevalence of neovascularisation compared to ACH- subjects (37% vs 6%, p=0.02) and a trend towards a higher prevalence of all individual markers, in particular thin-cap fibroatheroma (20% vs 0%, p=0.06). No differences were detected between patterns of coronary vasospasm. CONCLUSIONS: The presence of coronary vasospasm, regardless of its phenotype, is associated with higher lipid burden, plaque vulnerability and neovascularisation.
Therapeutic Advances in Cardiovascular Disease · 2012 · 1 citations · open access
Therapeutic procedures for coronary vasospasm-induced polymorphic ventricular tachycardia
AbstractCoronary vasospasm is an unusual cause of angina and myocardial ischemia, with the potential to provoke acute myocardial infarction, malignant cardiac arrhythmias, and sudden cardiac death. The diagnosis is largely clinical and requires a high index of suspicion. Provocation studies are rarely performed due to the risks of the procedure and the relatively low incidence of disease. A subset of patients does not respond to conventional medical therapy and a paucity of evidence exists to guide therapy. While generally believed a multifocal phenomenon, there have been reports of successful treatment of focal, refractory vasospasm with coronary stent implantation. Furthermore, consideration of an implantable cardioverter defibrillator is warranted when vasospasm is complicated by lethal ventricular arrhythmias.
Health and Ecology Issues · 2007 · 0 citations · open access
CURRENT STATE AND PROSPECT OF INTERVENTIONAL METHODS OF DIAGNOSTICS AND TREATMENT OF CORONARY VASOSPASM
AbstractCurrently coronary arteriography is widely used to establish the presence or absence of coronary stenoses, define therapeutic options, and determine prognosis in patients with symptoms or signs of ischemic coronary artery disease. Vasospastic angina indicates a form of angina caused by coronary artery spasm. The article reviews the most common difficulties and prospect of application of contemporary methods of diagnostics and treatment to find a solution of the task. The important tendency is development of percutaneous coronary interventions in treatment of coronary vasospasm.
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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