DeCure for Catecholaminergic polymorphic ventricular tachycardia 1
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for catecholaminergic polymorphic ventricular tachycardia 1 — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCatecholaminergic polymorphic ventricular tachycardia 1 maps to a 13-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 catecholaminergic polymorphic ventricular tachycardia 1 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
transient receptor potential cation channel subfamily M member 4 (TRPM4) — TRPM4 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 2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9MRT · 2.44 Å · ligand [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho
ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate (PT5). Experimental structure, not a prediction.
What the evidence adds up to
Catecholaminergic polymorphic ventricular tachycardia 1 is a rare genetic disorder caused by mutations in genes involved in intracellular calcium homeostasis in cardiac cells. Affected patients present with life-threatening ventricular arrhythmias triggered by emotional or physical stress. Diagnosis depends on demonstrating polymorphic or bidirectional ventricular tachycardia under adrenergic stress; genetic testing can be confirmatory in some patients. Mortality is high when untreated, and sudden cardiac death may be the first manifestation. First-degree relatives of a proband should be offered genetic testing if the causal mutation is known, or clinically evaluated with provocative testing if it is not.
A 2012 review states that in the absence of rigorous trials, prophylactic treatment of asymptomatic patients appears to reduce morbidity and mortality. No specific drug, dose, or survival numbers are given in that abstract. A 2006 review notes that abnormal calcium leak from the mutant cardiac ryanodine receptor has been associated with delayed afterdepolarisations, suggesting arrhythmogenesis in CPVT is likely induced by triggered activity. That review discusses implications for novel therapeutic strategies but reports no clinical trial results.
A 2020 review describes the mechanistic progression from beta-adrenergic stimulation to mono/polymorphic ventricular tachycardia and discusses current hypotheses about the cellular and tissue origin of the arrhythmias. No treatment outcomes, response rates, or survival data are reported in any of these three abstracts. What is still missing are randomised controlled trials in asymptomatic patients, validated biomarkers to stratify risk in mutation carriers, and funding for prospective studies that could replace the current reliance on expert opinion.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Future Cardiology · 2012 · 3 citations
Treatment of Asymptomatic Catecholaminergic Polymorphic Ventricular Tachycardia
AbstractCatecholaminergic polymorphic ventricular tachycardia is a rare genetic disorder caused by mutations in genes involved in the intracellular calcium homeostasis of cardiac cells. Affected patients typically present with life-threatening ventricular arrhythmias precipitated by emotional/physical stress. The diagnosis is based on the demonstration of polymorphic or bidirectional ventricular tachycardia associated with adrenergic stress. Genetic testing can be confirmatory in some patients. Treatment for catecholaminergic polymorphic ventricular tachycardia includes medical and surgical efforts to suppress the effects of epinephrine at the myocardial level and/or modulation of calcium homeostasis. Mortality is high when untreated and sudden cardiac death may be the first manifestation of the disease. First-degree relatives of a proband should be offered genetic testing if the causal mutation is known. If the family mutation is not known, relatives should be clinically evaluated with provocative testing. In the absence of rigorous trials, prophylactic treatment of the asymptomatic catecholaminergic polymorphic ventricular tachycardia patient appears to reduce morbidity and mortality.
AbstractCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac arrhythmia characterized by the presence of ventricular tachycardia in response to β-adrenergic receptor stimulation. Here, we describe the mechanistic progression from β-adrenergic stimulation to the formation of mono/polymorphic ventricular tachycardia. The goal of this review is to highlight the current molecular mechanisms that lead to CPVT followed by a discussion of the current hypotheses and research around the cellular/tissue origin of the arrhythmias.
Journal of Arrhythmia · 2006 · 0 citations · open access
Arrhythmogenic Mechanism of Catecholaminergic Polymorphic Ventricular Tachycardia
AbstractCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly lethal form of inherited arrhythmogenic disease characterized by adrenergically mediated polymorphic VT. The identification of the genetic substrate of the disease has allowed to achieve important milestones in the understanding of the arrhythmogenic mechanisms of the disease. Abnormal calcium leak from the mutant cardiac ryanodine receptor has been associated with the induction of delayed afterdepolarization suggesting that arrhythmogenesis in CPVT is likely to be induced by triggered activity. Here we review the current knowledge and some controversial issues about the molecular mechanism of arrhythmias initiation in CPVT and we discuss their implications for the development of novel therapeutic strategies in CPVT.
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.
