DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for heart conduction disease — screening already-approved drugs against its 30-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHeart conduction disease maps to a 30-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 heart conduction 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
lipoprotein(a) (LPA) — LPA 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8TCE · 1.07 Å · ligand (2S)-3-phenyl-2-[(3R)-pyrrolidin-3-yl]propanoic acid (HWF). Experimental structure, not a prediction.
What the evidence adds up to
Left bundle branch block affects roughly 25% of the heart failure population, and the 2006 review argues that the resulting intra-ventricular asynchrony may itself cause deterioration of cardiac function and remodelling, not merely accompany it. The review offers no trial data for any therapy.
A 2009 study of a single family with first-degree atrioventricular block found a novel SCN5A mutation, P1008S, that reduced peak sodium current to 11.77% of wild-type. The mutant channels were trapped inside cells and could not be rescued by incubation with mexiletine at 300 µM. A second variation in CACNB2b slowed inactivation of L-type calcium current. Using a computational model, the authors showed that the sodium current reduction alone could cause loss of the right ventricular epicardial action potential dome (a feature of Brugada syndrome), but that the calcium current change prevented that loss while still slowing conduction. This suggests that the combination of a sodium loss-of-function and a calcium gain-of-function can produce pure conduction disease without Brugada syndrome.
A 2017 review of cardiac conduction system lineages states that the components of the conduction system arise from separate early cell fate decisions, not a single lineage. It offers no therapeutic intervention.
The 2024 HeartPlus Clinic project treated 39 patients with stimulant-associated cardiomyopathy (most using methamphetamine) using guideline-directed heart failure drugs plus contingency management for stimulant use disorder. Of 25 who attended at least once, only 7 completed the 12-week programme. Among those 7, all improved their Kansas City Cardiomyopathy Questionnaire score by at least 10 points, and 4 of the 7 improved left ventricular ejection fraction by at least 10 percentage points. The programme cost $74 per participant. The sample is too small and the dropout rate too high to draw conclusions about efficacy; no randomised comparator exists.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Heart Failure · 2006 · 177 citations · open access
Left Bundle Branch Block as a Risk Factor for Progression to Heart Failure
AbstractThe prevalence of conduction disturbances, particularly left bundle branch block (LBBB), is strongly correlated with age and with the presence of cardiovascular disease. LBBB has been reported to affect approximately 25% of the heart failure (HF) population and it is likely that the deleterious role of such conduction disorders in the progression to HF has been underestimated. The purpose of this article is to review the data from the literature indicating that LBBB may have a causative role, mediated through the resulting intra-ventricular asynchrony, in the deterioration of cardiac function and the development of cardiac remodelling and HF. It also aims to address the potential for future clinical therapies for this conduction disorder.
Pacing and Clinical Electrophysiology · 2009 · 35 citations · open access
Dual Variation in <i>SCN5A</i> and <i>CACNB2b</i> Underlies the Development of Cardiac Conduction Disease without Brugada Syndrome
AbstractBACKGROUND: Inherited loss of function mutations in SCN5A have been linked to overlapping syndromes including cardiac conduction disease and Brugada syndrome (BrS). The mechanisms responsible for the development of one without the other are poorly understood. METHODS: Direct sequencing was performed in a family with cardiac conduction disease. Wild-type (WT) and mutant channels were expressed in TSA201 cells for electrophysiological study. Green fluorescent protein (GFP)-fused WT or mutant genes were used to assess channel trafficking. RESULTS: A novel SCN5A mutation, P1008S, was identified in all family members displaying first-degree atrioventricular block, but not in unaffected family members nor in 430 reference alleles. Peak P1008S current was 11.77% of WT (P < 0.001). Confocal microscopy showed that WT channels tagged with GFP were localized on the cell surface, whereas GFP-tagged P1008S channels remained trapped in intracellular organelles. Trafficking could be rescued by incubation at room temperature, but not by incubation with mexiletine (300 muM) at 37 degrees C. We also identified a novel polymorphism (D601E) in CACNB2b that slowed inactivation of L-type calcium current (I(Ca,L)), significantly increased total charge. Using the Luo-Rudy action potential (AP) model, we show that the reduction in sodium current (I(Na)) can cause loss of the right ventricular epicardial AP dome in the absence but not in the presence of the slowed inactivation of I(Ca,L). Slowed conduction was present in both cases. CONCLUSIONS: Our results suggest genetic variations leading to a loss-of-function in I(Na) coupled with a gain of function in I(Ca,L) may underlie the development of cardiac conduction disease without BrS.
Journal of Cardiovascular Development and Disease · 2017 · 14 citations · open access
Lineages of the Cardiac Conduction System
AbstractThe cardiac conduction system (CCS) initiates and coordinately propagates the electrical impulse to orchestrate the heartbeat. It consists of a set of interconnected components with shared properties. A better understanding of the origin and specification of CCS lineages has allowed us to better comprehend the etiology of CCS disease and has provided leads for development of therapies. A variety of technologies and approaches have been used to investigate CCS lineages, which will be summarized in this review. The findings imply that there is not a single CCS lineage. In contrast, early cell fate decisions segregate the lineages of the CCS components while they remain connected to each other.
Journal of the American Heart Association · 2025 · 9 citations · open access
Cardiac Conduction Disorders Due to Acquired or Genetic Causes in Young Adults: A Review of the Current Literature
AbstractCardiac conduction disorders can manifest in young adults in isolated forms, associated with myocardial diseases or as part of a multiorgan disorder. Underlying causes of cardiac conduction disorders may be genetically determined or acquired. Cardiac conduction disorder in young adults is a complex and often underestimated and underrecognized disease that may need of a multidisciplinary team for the diagnosis, treatment, and long-term management of these patients. Therefore, it is crucial to raise clinicians' awareness of this condition. In this review, we provide a comprehensive update on the cause, diagnosis, and treatment of young adults with cardiac conduction disorders, also suggesting potential strategies to improve the current clinical management of these patients.
Abstract 4142436: The HeartPlus Clinic Project: Multidisciplinary Treatment for Patients with Stimulant-Associated Cardiomyopathy
AbstractBackground: Stimulant-associated cardiomyopathy is an increasingly common cause of non-ischemic cardiomyopathy. Unfortunately, the last decade has seen dramatically higher rates of hospitalization for heart failure related to stimulant use. There are currently no Food and Drug Administration-approved medications for stimulant use disorder treatment (SUD). However, contingency management is a behavioral treatment that has been shown to be effective for SUD. In partnership with UC San Francisco, we developed a heart failure-addiction medicine co-management clinic (HeartPlus) to offer guideline-directed medical therapy in conjunction with contingency management to treat stimulant-associated cardiomyopathy over twelve weeks. The most common stimulant of abuse was methamphetamine. Methods: Our retrospective chart review assessed the feasibility of an Addiction Medicine and Heart Failure Cardiology co-management clinic at UC Davis. The clinic combined contingency management including point of care urine drug testing, as well as guideline-directed medical therapy for heart failure. We evaluated how many patients attended HeartPlus clinic at least once, how many completed the twelve-week program, and of those patients who completed the program, how many had improvement in self-reported symptoms as assessed by Kansas City Cardiomyopathy Questionaire (KCCQ-12) and left ventricular systolic function as assessed by echocardiogram. Results: A total of 39 patients were referred to HeartPlus Clinic. Of those referred, 25 patients attended the initial visit, and 7 patients successfully completed the 12-week program. Of the 7 patients who completed the program, 4 patients had improvement in left ventricular ejection fraction by at least ten percentage points. All 7 patients demonstrated improvement in KCCQ-12 scores by at least ten points (generally accepted as moderate improvement). Conclusions: The HeartPlus Clinic is a feasible treatment intervention for patients with stimulant-associated cardiomyopathy. For those patients who completed the program, they reported encouraging improvement in heart failure symptoms and four of seven demonstrated significant improvement in left ventricular systolic function. At an average cost of $74 per participant, this twelve-week multidisciplinary program is a promising area for future efforts to treat this growing population of disproportionately young patients.
Clinical observation on trimetazidine in treatment of chronic heart failure
AbstractObjective To explore the clinical effect of chlorpromazine(TMZ)in treatment of chronic heart failure(CHF).Methods 70 patients with CHF were randomly divided into control group and treatment group 35 cases in each gronp,control group was given conventional treatment,treatment group on the basis of additional application TMZ,20mg/times,3 times/d.8 weeks after the observation and comparison of two groups of cardiac function in improving the situation.Results Treatment group before the treatment of LVEF(38.0 ± 2.4)％ After treatment,LVEF(48.0 ±2.3)％ ;control group before treatment LVEF(38.2 ±2.2)％ after treatment,LVEF(42.0 t2.5)％ ;Twosets of treatment LVEFdifference statistically significant(t =6.9419,2.8482,allP ＜ 0.05); Treatment group compared with control groups after treatment improve even more obvious(t =4.3147,P ＜0.05)o Control groups and then hospitalized 10 cases(28.5％),the treatment group hospitalization 3 cases(8.5％),both groups rate difference statistically significant(x2 =4.629,P ＜0.05).Both groups were no deaths,no serious adverse effects.Conclusion General against heart failure therapy on the basis of the combined with TMZ could significantly improve the cardiac function of patients with chronic heart failure,reducing hospitalization rates.
Key words:
Heart failure, congestive; Heart function; Trimetazidine
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.
