DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for dilated cardiomyopathy 1V — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDilated cardiomyopathy 1V maps to a 1-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 dilated cardiomyopathy 1v 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
presenilin 2 (PSEN2) — PSEN2 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 pc1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7Y5X · 3.0 Å · ligand 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (PC1). Experimental structure, not a prediction.
What the evidence adds up to
Pathogenic variants in genes causing dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy were studied using single-nucleus RNA sequencing of 880,000 nuclei from 18 control and 61 failing non-ischemic human hearts. The resulting ventricular cell atlas showed distinct right and left ventricular responses, genotype-associated pathways, and differential gene expression, suggesting candidate therapeutic targets but no specific drug.
A review from 2002 noted that the origins of idiopathic dilated cardiomyopathy remain unclear, and clinicians face challenges in identifying and treating causes to improve symptoms and survival. A 2016 review identified causative genetic mutations in more than 40 genes encoding proteins from different cellular structures and pathways, but again offered no treatment.
Partial left ventriculectomy (PLV) was evaluated in 24 patients (12 idiopathic, 12 ischemic) with DCM. In-hospital deaths were 3 (12.5%). Over a mean follow-up of 26 months, there were 9 late deaths (38%), 6 in the idiopathic group. Five-year actuarial survival was 74% in the ischemic group and 33% in the idiopathic group. A literature review of 506 patients (255 idiopathic, 89 ischemic) reported 88 in-hospital deaths (17.4%), with 55 (62.5%) due to low cardiac output. Among 386 patients with late outcome data, there were 89 late deaths (22.9%), 50 (56.2%) from recurrence of congestive heart failure. One-year survival ranged from 50% to 85%, two-year survival from 45% to 72%, and three-year survival from 33% to 64%. The authors concluded that PLV has relatively high early mortality with satisfactory late results.
A 2006 review discussed familial and virus-induced DCM mechanisms, noting that discoveries in molecular genetics and virology might lead to gene therapy for familial cardiomyopathy and antiviral agents for virus-induced cardiomyopathy. No such therapies have been tested in the trials summarised here. What is still missing are completed clinical trials of gene therapy or antiviral agents in DCM, adequate patient stratification by genotype or viral status, and funding for such trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science · 2022 · 241 citations · open access
Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies
AbstractPathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single-cell resolution. Together, these data illuminate both shared and distinct cellular and molecular architectures of human heart failure and suggest candidate therapeutic targets.
Cleveland Clinic Journal of Medicine · 2002 · 44 citations
Idiopathic dilated cardiomyopathy: a common but mystifying cause of heart failure.
AbstractWhile researchers try to elucidate the origins of idiopathic dilated cardiomyopathy, clinicians continue to face the challenges of identifying and treating the causes of this condition to improve symptoms and survival. We review classification schemes for dilated cardiomyopathy and the current range of diagnostic and therapeutic options and treatment goals.
Ventricular adenine nucleotide translocator mRNA is upregulated in dilated cardiomyopathy
AbstractOBJECTIVE: A disturbed energy transfer involving the adenine nucleotide translocator across the inner mitochondrial membrane has been suggested to be one specific pathogenetic mechanism in dilated cardiomyopathy. Pretranslational steady state expression of this protein in dilated cardiomyopathy was investigated. METHODS: Concentrations of adenine nucleotide translocator were quantified by solution hybridisation. The enzyme or protein expressions of citrate synthase, lactate dehydrogenase, and creatine kinase with isozymes were determined. Analysis was performed on specimens from the left and right ventricles from six organ donor hearts, six explanted hearts with dilated cardiomyopathy, two explanted hearts with ischaemic cardiomyopathy, and from papillary muscles from seven patients operated on for mitral regurgitation. RESULTS: The ejection fraction in patients with mitral regurgitation was 50(10)%, significantly higher (p < 0.001) than in patients with dilated cardiomyopathy (23(5))%. In mitral regurgitation and in ischaemic cardiomyopathy left ventricular adenine nucleotide translocator mRNA concentrations did not differ from those in donor hearts. In dilated cardiomyopathy, adenine nucleotide translocator mRNA concentrations were significantly increased (p < 0.001). Upregulation was more pronounced in right ventricular than in left ventricular myocardium (p < 0.01). The lactate dehydrogenase M subunit fraction was increased to a similar degree in dilated cardiomyopathy and in mitral regurgitation (p < 0.05). Citrate synthase activity was significantly decreased only in dilated cardiomyopathy (p < 0.005). On the other hand, the creatine kinase B subunit content was significantly higher in mitral regurgitation than in dilated cardiomyopathy (p < 0.001). CONCLUSIONS: Despite signs of increased anaerobic and depressed oxidative capacities, dilated cardiomyopathy was specifically characterised by pretranslational upregulation of adenine nucleotide translocator.
Early and Late Results of Partial Left Ventriculectomy: Single Center Experience and Review of the Literature
AbstractAIM: To evaluate early and late outcome of partial left ventriculectomy (PLV) in a single center and to conduct a review of the literature. METHODS: From February 1996 to August 2001, 24 patients with dilated cardiomyopathy (DCM) (12 idiopathic, 12 ischemic) underwent PLV. Perioperative and follow-up data were prospectively entered into a database and analyzed. An observational analysis of the literature was carried out of all the published series of PLV reporting on > or =15 patients. RESULTS: In our series there were 22 males with amean age of 65 years (range 49 to73). Of the 22, there were 3 (12.5%) in-hospital deaths. Mean duration of follow-up was 26 months (range 3 to 71) with 9 late deaths (38%), 6 in the idiopathic group. The five-year actuarial survival was 74% in the ischemic group and 33% in the idiopathic group. The observational analysis of literature included a total of 506 patients (425 males, age 50.2 +/- 5.2 years)]. The etiology was idiopathic in 255 (50.4%), and ischemic in 89 (17.6%) patients. Baseline characteristics of the whole population include: ejection fraction 18.9 +/- 3.9%, NYHA functional class 3.7 +/- 0.2, and LVEDD of 7.7 +/- 0.4 cm. Severe mitral regurgitation was present in 368 (72.7%) patients. There were 88 (17.4%) in-hospital deaths. Cause of death included 55 due to (62.5%) low cardiac output, 10 (11.3%) due to severe bleeding, 7 (7.95%) caused by malignant arrhythmias, 8 (9%) due to sepsis, and 5 (5.7%) as a result of stroke. Ten of the selected series (overall 386 patients) reported late outcome. There were 89 (22.9%) late deaths, 12 (13.5%) were not cardiac-related, 50 (56.2%) were due to recurrence of congestive heart failure (CHF), 20 (22.5%) caused by sudden arrhythmias, 5 (5.6%) due to infections, and 2 (2.2%) from strokes. Overall, there were 248 (64.2%) survivors, of whom 179 (72.17%) were reported to be in NYHA functional class I or II. All 10 papers reported one-year survival ranging from 50% to 85%. Seven reported a two-year survival of 45% to 72%, and 4 reported a three-year survival of 33% to 64%. CONCLUSIONS: Our results and the review of the literature seem to suggest a relatively high early mortality with satisfactory late results of PLV in patients with dilated cardiomyopathy.
Journal of Cardiovascular Medicine · 2016 · 15 citations
Genetic bases of dilated cardiomyopathy
AbstractCardiomyopathies represent a wide and heterogeneous group of diseases wherein a genetic cause has been consistently identified.Dilated cardiomyopathy (DCM) is characterized by ventricular dilation and progressive systolic dysfunction, and it is the most common form of cardiomyopathy.Causative genetic mutations have been identified in more than 40 genes encoding proteins belonging to different cellular structures and pathways.A great diversity of pathways has been implied in the pathogenesis of DCM, depending on the affected genes and on the dislodged intracellular structures or mechanisms.This review describes the major genes and focus on the pathophysiologic mechanisms of DCM, with a special consideration of the most recent discoveries in the field.
Current Opinion in Cardiology · 1991 · 1 citations
Dilated cardiomyopathy
AbstractDilated cardiomyopathy is the most common form of cardiomyopathy and is anatomically defined by large atrial and ventricular chambers, thin or normal myocardial walls, and poor systolic function. In the United States, up to 10,000 deaths every year have been determined to be secondary to cardiomyopathy, and of these 80% were due to the dilated form of the disease. This review describes recent advances of DCM, which can be grouped into the following headings: 1)etiologies and mechanisms of disease; 2) pathophysiology of the dilated heart; 3) diagnostic approaches; 4) clinical findings and prognosis; and 5) therapy.
Current Opinion in Organ Transplantation · 2006 · 1 citations
Mechanisms of idiopathic dilated cardiomyopathies
AbstractPurpose of review Dilated cardiomyopathy is a disease of the heart muscle, characterized by ventricular dilation and depressed myocardial contractility in the absence of abnormal loading conditions or ischemic heart disease. Dilated cardiomyopathy may be viewed as a progressive disorder that is initiated after an ‘index event’ damages the heart muscle, thereby preventing the heart from contracting normally. This review will discuss the mechanisms of dilated cardiomyopathy, with special focus on familial dilated cardiomyopathy and virus-induced dilated cardiomyopathy. Recent findings In the past few years, discoveries in molecular genetics and virology have offered insights into the pathomechanisms of dilated cardiomyopathy. Summary The increasing knowledge of a potential causal link between genetic mutations and viral infections and the development of dilated cardiomyopathy may lead to a breakthrough in the treatment of the disease. In particular, the development of gene therapy to treat familial cardiomyopathy and the development of antiviral agents to treat persistent viral infections in virus-induced cardiomyopathy could greatly enhance the treatment of dilated cardiomyopathy.
Targeted ACE inhibitors for the Treatment of Dilated Cardiomyopathy (DCM)
AbstractDilated cardiomyopathy, a subtype of cardiomyopathies characterized by ventricular dilation, particularly of the left or both ventricles, coupled with systolic impairment, represents a heterogeneous condition distinct from valvular heart disorders, congenital cardiac anomalies, hypertensive cardiomyopathy, and acyanotic heart diseases. This article explores the varied categories of angiotensin-converting enzyme (ACE) inhibitors and their precise molecular targets. As a relatively uncommon disease entity, dilated cardiomyopathy lacks a definitive pharmacological cure and is managed primarily through medical therapy or surgical interventions. Emerging therapeutic modalities, such as left ventricular assist device (LVAD) support, have been introduced, yet the majority of these treatments necessitate careful consideration due to their specific indications and potential implications. Keywords: dilated cardiomyopathy, drug targeting, ACE inhibitors
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.
