DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for heart septal defect — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHeart septal defect maps to a 4-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 septal defect 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
ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) — ABL1 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 myrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1OPL · 3.42 Å · ligand MYRISTIC ACID (MYR). Experimental structure, not a prediction.
What the evidence adds up to
In A/J mice atrial septal defect occurs spontaneously and can be produced by dextroamphetamine; in C57BL/6J mice the same is true for ventricular septal defect. These strains are proposed as animal homologies for the human congenital diseases, allowing study of how nongenetic factors push genetically predisposed individuals past a threshold for a specific cardiac malformation. No human data on dextroamphetamine and septal defects are given in this 1968 abstract.
Cardiac septation defects are among the most common human birth defects. The genetic factors identified are mostly transcription factors active in early cardiogenesis, and modifying these genes in animal models is clarifying common pathways that lead to diverse cardiac defects. The 2006 abstract states that understanding these processes should eventually lead to molecular-based treatment and prevention, but no such treatments are described.
A single-centre review from 2004–2005 examined current management of isolated ventricular septal defect at The Children’s Hospital, Denver, but the abstract reports no numerical results, no comparison of surgical versus non-surgical outcomes, and no evidence base for when repair is needed. For post-myocardial infarction ventricular septal defect, a retrospective study of 20 patients operated between 2010 and 2018 reported 45% mortality. Non-survivors were all in cardiogenic shock, had emergency or salvage operations, preoperative mechanical ventilation, shorter time from intra-aortic balloon pump insertion to surgery, shorter time from defect to surgery, more postoperative renal replacement therapy, and more residual defects. In multivariate analysis, preoperative mechanical ventilation, postoperative renal replacement therapy, and residual defect were strong predictors of hospital mortality. The authors suggest that initial stabilisation and delayed repair, when possible, may improve outcome.
A separate 2010 case report describes a hybrid surgical and percutaneous approach for a recurrent post-infarction ventricular septal defect, but gives no survival or complication data beyond the single patient. What remains missing are prospective trials that stratify patients by genetic risk, haemodynamic status, and timing of intervention, and adequate funding to test whether delayed repair or percutaneous closure reduces the high mortality seen in the surgical series.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Teratology · 1968 · 43 citations
Homologies for congenital heart diseases: Murine models, influenced by dextroamphetamine
AbstractAbstract The spontaneous occurrence and teratogenic production of atrial septal defect in A/J mice and ventricular septal defect in C57BL/6J mice lead to the proposal that these strains may represent animal homologies of these congenital heart diseases in human beings. Such models permit investigation into the mechanisms by which nongenetic factors cause genetically predisposed individuals to reach a particular threshold of developmental abnormality and develop a specific type of cardiac malformation.
Journal of Clinical Investigation · 2005 · 21 citations · open access
Genetic causes of human heart failure
AbstractFactors that render patients with cardiovascular disease at high risk for heart failure remain incompletely defined. Recent insights into molecular genetic causes of myocardial diseases have highlighted the importance of single-gene defects in the pathogenesis of heart failure. Through analyses of the mechanisms by which a mutation selectively perturbs one component of cardiac physiology and triggers cell and molecular responses, studies of human gene mutations provide a window into the complex processes of cardiac remodeling and heart failure. Knowledge gleaned from these studies shows promise for defining novel therapeutic targets for genetic and acquired causes of heart failure.
Annals of Pediatric Cardiology · 2015 · 14 citations · open access
Infective endocarditis following coil occlusion of perimembranous ventricular septal defect with the Nit-Occlud <sup>(®)</sup> Le device
AbstractThe Nitinol coil system was recently developed by "PFM" specifically for the transcatheter occlusion of ventricular septal defects (VSD). The device consists of a coil fitted with polyester fibers designated for the closure of perimembranous defects with an aneurysmal septum and some muscular VSDs. We report a case of fatal acute infective endocarditis 10 days following the procedure.
Genetics of Cardiac Septation Defects and Their Pre-Implantation Diagnosis
AbstractCardiac septation defects are among the most common birth defects in humans. The frequency of these defects reflects the complexity of cardiogenesis, which involves such processes as cell proliferation, migration, differentiation, and morphogenetic interactions. Major advances in the understanding of the underlying genetic etiologies of cardiac septation defects have provided insight into the genetic pathways involved. These genetic factors are most often transcription factors involved in the early stages of cardiogenesis. The ability to modify these genes in animal models is providing a better understanding of the role of these genes in common pathways leading to diverse forms of cardiac defects. Ultimately, our understanding of these basic processes should lead to molecular-based treatment and prevention options for those individuals most at risk for such birth defects.
AbstractAt this time, the current practice for treatment of patients with isolated ventricular septal defect is infrequently studied. With this in mind, it was our intent to assess the current management of ventricular septal defect at a single center, The Children's Hospital, Denver. We reviewed the practice at this institution to determine if there is an evidence base for when or if a patient with an isolated ventricular septal defect requires surgical repair. With approval from the Colorado Multiple Institutional Review Board (protocol # 06-0097), we reviewed the data on patients with isolated ventricular septal defect seen during the calendar years of 2004 and 2005, determining the state of the patients, and the level of intervention through December 31, 2005.
Bratislavské lekárske listy/Bratislava medical journal · 2021 · 1 citations · open access
Mortality and risk factors after a surgical repair of postinfarction ventricular septal defect
AbstractBACKGROUND: The aim of this study was to present our experience in the treatment of post-myocardial infarction ventricular septal defect and examine the various risk factors. METHODS: This is a retrospective study. From January 2010 to December 2018, 20 patients underwent an urgent /emergency surgical repair of post-myocardial infarction ventricular septal defect. RESULTS: The mortality in our group of patients was 45 %. Non-survivors compared to the survivors were all in cardiogenic shock (p=0.0098), had an emergency/salvage operation (p=0.0055), preoperative mechanical ventilation (p=0.0081), shorter time between intraaortic balloon pressure insertion and surgery (p=0.0115), shorter median time between ventricular septal defect and surgery, postoperative renal replacement therapy (p=0.0498), and more patients had a residual effect (p=0.0022). In multivariate analysis, preoperative mechanical ventilation (p=0.0001), postoperative renal replacement therapy (p=0.0021) and residual defect (p=0.0000027) were shown to be strong predictors for hospital mortality. CONCLUSION: This analysis showed that post-myocardial infarction ventricular septal defect repair is a devastating complication and preoperative mechanical ventilation, postoperative renal replacement therapy and residual defect were identified to be the predictors of mortality. Initial stabilization of the patients, when it is possible, and a delayed repair, may improve the outcome of these patients (Tab. 3, Ref. 17).
Bulletin of the American Physical Society · 2010 · 0 citations
Electronic Correlation in strongly driven atomic and molecular systems
AbstractDevelopment of ventricular septal defect (VSD) is a rare but serious complication of transmural myocardial infarction (MI). The incidence of post-MI VSDs is reduced significantly with thrombolytic therapy, yet mortality remains high. Surgical repair is difficult and can be complicated by a recurrent VSD in some cases. Percutaneous catheter-based closure techniques can be used to treat these patients. This case report demonstrates the successful application of a hybrid approach utilizing initial surgical and subsequent percutaneous techniques for the recurrence in the treatment of a post-MI VSD.
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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