DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for left ventricular noncompaction — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLeft ventricular noncompaction maps to a 31-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 left ventricular noncompaction 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
LIM domain binding 3 (LDB3) — LDB3 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 gludrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4YDP · 1.4 Å · ligand GLUTAMIC ACID (GLU). Experimental structure, not a prediction.
What the evidence adds up to
No specific drug therapy exists for left ventricular noncompaction itself. A 2010 review states that treatment is instead directed at symptoms, disease progression, and complications, and is modelled on the approach for dilated cardiomyopathy, including heart failure drugs, arrhythmia management, and oral anticoagulation for emboli prevention. The same review notes that specific treatments are not available for most patients and that major challenges remain in detecting early disease, identifying the mechanism of left ventricular dysfunction, and developing treatments that target the initiating cause.
A 2022 case report describes a 58-year-old woman with left ventricular noncompaction and heart failure who had responded poorly to four years of treatment with metoprolol, benazepril, torasemide, spirolactone, and digoxin. On presentation her left ventricular ejection fraction was 26% with class IV diastolic dysfunction, and cardiac magnetic resonance imaging showed a noncompacted-to-compacted myocardium ratio of 3.9. She was given sacubitril-valsartan (100 mg/day, later increased to 200 mg/day) added to a beta-blocker, torasemide, spirolactone, digoxin, and isosorbide. Symptoms improved rapidly and she was discharged after one week. At 16 months, ejection fraction was 51% and the noncompacted-to-compacted ratio had fallen to 2.8. This is a single case, not a controlled trial.
A 2002 surgical series of 26 patients with sustained monomorphic ventricular tachycardia of left ventricular origin included two patients with non-ischaemic VT who were significantly younger, had lower NYHA class, and had better ejection fractions (mean 59.5%) than the 24 ischaemic patients. In those two patients there was no operative mortality and no recurrence of VT. The ischaemic group had an operative mortality of 8.3%, and 10-year freedom from recurrence or inducibility of VT among operative survivors was 78.8%. Survival in the whole series was 54.1% at 5 years and 43.3% at 10 years, with no arrhythmic or sudden cardiac deaths. The authors note that economic factors precluded implantable cardioverter-defibrillator use in most of these patients.
A 2007 review of the genetics of left ventricular noncompaction lists known associated genes (TAZ, DTNA, LDB3, LMNA, SCN5A, MYH7, MYBPC3) and additional loci suggested by linkage studies, but states that large studies have failed to identify the aetiology in the majority of patients. A 2025 bioinformatics analysis of two gene expression datasets identified four core genes (Col1a2, Postn, Timp1, Dcn) that were highly expressed in left ventricular noncompaction tissue samples, and the authors suggest Col1a2 and Postn as potential molecular targets, but no therapeutic intervention based on these targets has been tested. What remains missing is a clear genetic or molecular target validated in patients, a randomised trial of any drug specifically for left ventricular noncompaction rather than for heart failure generally, and a method to stratify patients by the predominant mechanism of their left ventricular dysfunction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Pediatrics · 2007 · 105 citations
Noncompaction of the left ventricle: primary cardiomyopathy with an elusive genetic etiology
AbstractPURPOSE OF REVIEW: Noncompaction of the left ventricle is a descriptive anatomical term and recently recognized primary cardiomyopathy. Cardiac imaging now allows for prompt detection. The specific etiology remains poorly understood, however, and the major genetic determinants are unknown. This review describes recent data showing the genetic heterogeneity and overlap with other cardiomyopathies. Understanding the genetics may depend on clarifying the distinctive diagnostic features and investigating the contribution of all known cardiomyopathy-causing genes with overlapping morphology. RECENT FINDINGS: Adding to the known genes (TAZ, DTNA, LDB3 and LMNA), recent work has identified SCN5A, MYH7 and MYBPC3 as associated loci. LDB3 may also be a genetic modifier. Case reports and linkage studies suggest additional loci at 1p36, 1q43 and 11p15. Aside from Barth syndrome, other genetic and metabolic syndromes with noncompaction have been described. Despite this, large studies have failed to identify the etiology in the majority of patients. SUMMARY: Despite advances in detection, comprehensive clinical, pathological, genetic, and family studies are necessary to define the phenotypic overlap with other cardiomyopathies. Without a more precise understanding of its etiology, the answers to the questions regarding the clinical relevance and management of patients with noncompaction of the left ventricle will remain elusive.
European Journal of Cardio-Thoracic Surgery · 2002 · 14 citations · open access
Surgery for ventricular tachycardia of left ventricular origin: risk factors for success and long-term outcome
AbstractOBJECTIVES: To review 26 consecutive patients with sustained monomorphic ventricular tachycardia (VT) of left ventricular origin, who underwent direct VT surgery. METHODS: Economic factors precluded the use of an implantable cardioverter defibrillator (ICD) in the majority of these patients, and the indication for surgery in 81% of patients was for failed medical drug therapy and 27% of patients had frequent or incessant life-threatening VT. The principles of direct VT surgery included intraoperative mapping, extended endocardial resection, cryoablation, left ventricular aneurysm repair by left ventricular remodelling and endoaneurysmorrhaphy, as well as coronary artery bypass grafting. RESULTS: Two patients with non-ischaemic VT were significantly younger (37.7 +/- 19.4 years, P = 0.03), had lower preoperative New York Heart Association class (P = 0.03), and had better left ventricular ejection fractions of 59.5 +/- 2.1% (P = 0.001) than the 24 ischaemic patients. No operative mortality or recurrence of VT occurred in this group. Ischaemic VT patients had an operative mortality of 8.3%; risk factors were concomitant valve surgery (P = 0.02), and perioperative intra-aortic balloon pump (P = 0.02). Surgery improved the left ventricular ejection fraction from 28.4 +/- 9.8% to 43.2 +/- 8.2% (P = 0.0001). Freedom from recurrence or inducibility of VT in operative survivors was 78.8 +/- 9.6% at 10 years; risk factors were arrhythmic focus remote to the left ventricular aneurysm (P = 0.015), and simple cryoablation or endocardial resection alone and not in combination (P = 0.003). Survival was 54.1 +/- 11.6% and 43.3 +/- 13.4% at 5 and 10 years, respectively, and there were no arrhythmic or sudden cardiac deaths. Patients with immediately life-threatening VT unsuitable for ICD implantation requiring urgent or emergent VT surgery had a 10-year survival of 22.2 +/- 13.9% compared to the more elective surgical group with a rate of 73.3 +/- 13.9% (P = 0.08). CONCLUSIONS: Direct VT surgery should remain an objective for symptomatic drug refractory VT of left ventricular origin.
The Treatment of Noncompaction of Ventricular Myocardium
AbstractAIMS: Critically reexamine and place in perspective the most appropriate therapeutic strategies for patients noncompaction of ventricular myocardium. RESULTS: Specific treatments are not available for the majority of patients with noncompaction of ventricular myocardium currently. Treatment of patients with noncompaction of ventricular myocardium could be similar to patients with other cardiomyopathies, especially dialated cardiomyopathy, and therefore, the primary aims of treatment are to control symptoms, disease progression, and complications, which should include appropriate treatment for heart failure, management of arrhythmias, and oral anticoagulation to prevent systemic emboli. CONCLUSION: Among the many challenges facing clinicians treating patients with noncompaction of ventricular myocardium are the detection of early disease, the identification of the predominant mechanism of left ventricular dysfunction, and the development of treatments that target the initiating mechanism of disease. Nevertheless, there have been major advances in our understanding of the genetic basis of noncompaction of ventricular myocardium, and recent advances in the drug therapy and nondrug therapy of noncompaction of ventricular myocardium have substantially improved the outlook for many patients. The rapid pace of current research and the development of new treatments for the management of both early and late disease augur well for the future.
Frontiers in Pediatrics · 2023 · 6 citations · open access
Advances in symptomatic therapy for left ventricular non-compaction in children
AbstractLeft ventricular non-compaction is a complex cardiomyopathy and the third largest childhood cardiomyopathy, for which limited knowledge is available. Both pathogenesis and prognosis are still under investigation. Currently, no effective treatment strategy exists to reduce its incidence or severity, and symptomatic treatment is the only clinical treatment strategy. Treatment strategies are constantly explored in clinical practice, and some progress has been made in coping with the corresponding symptoms because the prognosis of children with left ventricular non-compaction is usually poor if there are complications. In this review, we summarized and discussed the coping methods for different left ventricular non-compaction symptoms.
Cardiology Plus · 2022 · 3 citations · open access
Sacubitril-valsartan therapy in a patient with heart failure due to isolated left ventricular noncompaction: a case report and literature review
AbstractAbstract Background: Left ventricular noncompaction (LVNC) is a rare type of cardiomyopathy. The core clinical feature is heart failure that responds poorly to treatments. Case presentation: A 58-year-old woman received various treatments (including metoprolol, benazepril, torasemide, spirolactone, and digoxin) for 4 years for LVNC, but responded poorly. Upon presentation, transthoracic echocardiogram (ECHO) showed 26% left ventricular ejection fraction (LVEF) and class IV diastolic dysfunction. Upon cardiac magnetic resonance imaging (CMRI), the ratio of noncompacted versus compacted myocardium was 3.9. She received guideline-recommended treatments that included sacubitril-valsartan (100 mg/day) in addition to β-blocker, torasemide, spirolactone, digoxin, and isosorbide. Symptoms and signs improved rapidly, and she was discharged 1 week later. Sacubitril-valsartan dosage was adjusted to 200 mg/day 4 weeks later. She remained in relatively good health thereafter. At the last follow-up 16 months later, LVEF was 51% on ECHO. CMRI showed the significantly reduced ratio of 2.8 in noncompacted versus compacted myocardium. Conclusions: Sacubitril-valsartan therapy may result in reverse remodeling and improve long-term outcomes in LVNC patients.
Journal of Cardiothoracic Surgery · 2025 · 2 citations · open access
Role of Col1a2 and Postn in left ventricular noncompaction cardiomyopathy
AbstractBACKGROUND: Left ventricular noncompaction cardiomyopathy (LVNC) is a rare myocardial developmental anomaly characterized by incomplete myocardial compact layer development in the left ventricular wall, resulting in a multilayered trabeculated myocardium. METHODS: The datasets GSE71912 and GSE113251 of left ventricular noncompaction cardiomyopathy were downloaded from the gene expression omnibus (GEO) database generated from GPL13912 and GPL11002 platforms. Batch normalization was performed, followed by differentially expressed genes (DEGs), principal component analysis (PCA), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks. Heatmaps of gene expression levels were generated. Correlation with core genes was explored through comparative toxicogenomics database (CTD) analysis. RESULTS: A total of 500 DEGs were identified. WGCNA with a soft threshold power of 16 generated three modules. Hierarchical clustering dendrograms were constructed for all genes, identifying 4 core genes (Col1a2, Postn, Timp1, Dcn). These core genes were validated through enrichment analysis using Metascape. Heatmaps revealed high expression of core genes (Col1a2, Postn, Timp1, Dcn) in left ventricular noncompaction cardiomyopathy tissue samples. CTD analysis linked core genes (Col1a2, Postn, Timp1, Dcn) with conditions such as left ventricular hypertrophy, arrhythmias, heart diseases, heart failure, myocardial ischemia, vascular diseases, and inflammation. CONCLUSION: Col1a2 and Postn are significantly upregulated in left ventricular noncompaction cardiomyopathy, suggesting their potential role as molecular targets.
AbstractFelodipine is a new calcium antagonist with a high degree of vascular selectivity. Its potential role in the treatment of congestive heart failure was examined in short and long term oral studies. Short term felodipine 5 to 15 mg in 11 patients increased (p less than 0.001) cardiac index (from 2.1 +/- 0.1 to 3.3 +/- 0.2 L/min/m2), and reduced systemic resistance (from 26 +/- 2 to 12 +/- 2 units) and left ventricular end-diastolic pressure (from 26 +/- 2 to 13 +/- 2mm Hg) without affecting heart rate. Left ventricular max dp/dt did not change, but max dp/dt/p increased from 19 +/- 1 to 24 +/- 1 sec-1 (p less than 0.001). Left ventricular unloading was reflected by a shift in the end-systolic pressure-dimension relationship downwards and to the left. Myocardial oxygen supply to demand ratio improved significantly; coronary flow increased from 141 +/- 11 to 176 +/- 15 ml/min and myocardial oxygen consumption fell from 18 +/- 2 to 14 +/- 1 ml/min (p less than 0.05). Long term therapy with felodipine 30 mg daily in 10 patients improved treadmill exercise tolerance after 4 weeks by 24% (p less than 0.001). Stroke index at submaximal exercise increased from 37 +/- 3 to 47 +/- 2 ml/beat/m2 (p less than 0.001). Pulmonary capillary wedge pressure fell significantly (22 +/- 5 to 10 +/- 3mm Hg), as did arteriovenous oxygen difference (12.7 +/- 0.9 to 9.7 +/- 0.6 vols/100ml). Importantly, these beneficial effects with felodipine were sustained during 4 weeks' therapy without evidence of tachyphylaxis. These data indicate that the selective vasodilator properties of felodipine may extend the clinical application of calcium antagonists to include the management of heart failure.
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.
