DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for third-degree atrioventricular block — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThird-degree atrioventricular block maps to a 3-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 third-degree atrioventricular block 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
spectrin repeat containing nuclear envelope protein 1 (SYNE1) — SYNE1 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6R15 · 1.82 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
In a 2023 study of 84 patients with unstable third-degree atrioventricular block, isoprenaline infusion produced an effective clinical response in 84% of patients, compared with 31% for dopamine (p < 0.001). The drug was safe and tolerated, with no induced arrhythmias or hypotension, and reduced the need for temporary artificial pacing while patients awaited definitive pacemaker implantation. The study excluded asymptomatic patients and those with reversible causes of the block.
A 2021 case report describes a male patient with inferior myocardial infarction and total atrioventricular block who showed a marked reduction in heart rate after first and second doses of atropine — a paradoxical worsening of the block. The authors note that atropine has been associated with proarrhythmic effects, worsening of high-grade block, and worsening of ischaemia, and that immediate revascularisation may be the only required management in such cases.
A 2009 case report describes a patient with atrioventricular block compensated by a functional accessory pathway for 28 years. Over time the accessory pathway’s conduction properties at rest deteriorated, and at age 46 the patient became symptomatic and required a dual-chamber pacemaker. The authors caution that such concealed AV block must be recognised before radiofrequency ablation.
A 2024 review of congenital complete atrioventricular block in fetuses notes that steroids are the most used and most studied medications, and that their use has decreased the development of hydrops and prevented progression from type II to complete block. However, steroids can also cause oligohydramnios and fetal damage. The authors state that the use of beta-adrenergic stimulators, plasma, and other treatments remains controversial, with no clear evidence whether they should be used alone or in combination.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Cardiovascular Development and Disease · 2023 · 5 citations · open access
Efficacy and Safety of Isoprenaline during Unstable Third-Degree Atrioventricular Block
AbstractUnstable and symptomatic complete atrioventricular block represents a potentially fatal condition that requires prompt therapy while waiting for definitive pacemaker implantation. Although transcutaneous pacing is included in acute management, it could be a difficult approach due to its painfulness and the occasional failure of mechanical capture. Drug therapy is a feasible choice, and current guidelines encompass the use of atropine, dopamine, or epinephrine. Isoprenaline has never been investigated in this setting, and no specific indication of its use has been provided despite its potentially more favorable pharmacological profile. The study population included a consecutive series of patients who presented to the emergency department because of unstable third-degree atrioventricular block and were treated with either isoprenaline or dopamine infusion while waiting for definitive pacemaker implantation. Asymptomatic patients or those with reversible causes of complete atrioventricular block were excluded. The clinical response to the drug was deemed poor if, despite achieving a full drug dose, patients remained symptomatic and/or with hemodynamic instability, ventricular rate and rhythm did not improve or worsened, including if ventricular arrhythmias or asystolic pauses and/or irrepressible nausea/vomiting occurred. Isoprenaline infusion has proved to be safe and tolerated with no arrhythmia induction or hypotensive issues. Isoprenaline has also proven to be more satisfactory in achieving an effective clinical response in 84% of patients rather than dopamine (31%, p < 0.001), reducing the need for temporary artificial pacing. Our data point out the efficacy and safety of isoprenaline infusion and its greater tolerability over dopamine in the acute management of unstable third-degree AV block while waiting for definitive pacemaker implantation.
Pacing and Clinical Electrophysiology · 2009 · 3 citations
Compensatory Accessory Pathway for Complete Atrioventricular Block: 28‐Year Follow‐Up
AbstractWe report a case of atrioventricular (AV) block diagnosed 28 years ago compensated by a functional accessory pathway. During follow-up, the accessory pathway conduction properties at rest deteriorated while the refractory properties were unchanged. At 46 years, the patient became symptomatic from bradycardia and a dual-chamber pacemaker was implanted. Although rare, concealed AV block due to an accessory pathway has to be recognized before radiofrequency ablation.
Bali Journal of Anesthesiology · 2021 · 1 citations · open access
Paradoxical Heart Rate Response After Atropine Sulfate Administration in Total Atrioventricular Block Complicating Acute Myocardial Infarction
AbstractAbstract Acute myocardial infarction is sometimes complicated by atrioventricular block. Advanced cardiac life support guideline for the treatment of atrioventricular block suggests early use of atropine. Atropine works as a parasympatholytic drug that enhances SA node automaticity and AV node conduction. We report a case of a male patient with inferior myocardial infarction and total atrioventricular block who showed a marked reduction in heart rate after first and second atropine administration, a paradoxical worsening of the block. Atropine has been associated with some adverse consequences, including proarrhythmic effect, worsening of the high-grade atrioventricular block, and worsening of the ischemic situation. In this case of total atrioventricular block caused by acute myocardial infarction, immediate revascularization can be the only required management. Awareness of this potential adverse reaction will help the clinician make a risk/benefit ratio consideration regarding the use of atropine for certain patients.
Archivos de cardiología de México · 2024 · 0 citations · open access
Caracterización clínica de los pacientes con bloqueo atrio-ventricular completo fetal
AbstractThe following article seeks to describe the clinical characterization of patients with congenital complete atrioventricular block. Information was collected from different sources, among which is the presentation of the pathology and its impact on the fetus, and the main basis was look for an association between the use of medications and its prognosis. Within the treatment to be used in patients with fetal atrioventricular block, the use of steroids, beta-adrenergic stimulators, plasma, etc., is mentioned; however, their use is controversial, since there are still many studies in which it is not defined whether they are used in isolation or together to improve the patient's condition. Steroids are the medications most used in this pathology and also the most studied, although their use has decreased the development of hydrops and preventing a type II atrioventricular block from progressing to a complete one, it can also cause greater loss of amniotic fluid, causing oligohydramnios that could cause fetal damage. Due to this, the assessment of the use of different medications will depend on the patient's clinical condition and multidisciplinary management should be addressed in the perinatal period to improve the prognosis of the patient and the mother.
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.
