DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for dilated cardiomyopathy 1X — 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 1X 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 1x 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.
What the evidence adds up to
A 1994 follow-up of 235 patients aged 16–70 with dilated cardiomyopathy, enrolled from 1978 to 1992, showed that two-year survival rose from 73.8% in the 1978–1982 period to 87.7% in 1983–1987 and 90.3% in 1988–1992. Four-year survival increased from 53.8% to 72.3% to 82.9% across the same periods. The authors note that patients in later periods were younger and less severely affected, which partly explains the improvement. After stratifying for disease severity, survival differences remained significant, suggesting treatment had a sustained effect. A progressively higher proportion of patients received ACE inhibitors and later beta blockers. In the 1983–1987 group, patients treated with ACE inhibitors showed better survival than those not treated, after stratification for heart failure severity. In the 1988–1992 group, beta blockers had a significant additive effect with conventional therapy: four-year survival in patients with mild and moderate-to-severe heart failure treated with beta blockers, usually digitalis and ACE inhibitors, was 90% and 87.5% respectively.
A 2019 study examined a specific familial dilated cardiomyopathy mutation in troponin-T, ΔK210. The authors determined the molecular mechanism and used computational modelling to predict that the mutation should reduce force per sarcomere. In mutant cardiomyocytes, ΔK210 not only reduced contractility but also caused cellular hypertrophy and impaired the cells’ ability to adapt to changes in substrate stiffness, such as the fibrosis that occurs with aging and disease. The authors implicate altered mechanosensing as an important factor in the development of DCM.
A 2023 review states that an estimated 40% of familial dilated cardiomyopathy cases have an identifiable genetic cause. Many gene mutations have been identified, and particular genes affecting cell-cell junctions and the cytoskeleton are associated with increased risk of arrhythmias and sudden cardiac death. The review notes that identification of genetic DCM has improved through next-generation sequencing and cardiac imaging, and that precision medicine is now at the forefront of treatment. It states that patients with genetic cardiomyopathy stand to benefit from gene mechanism-specific therapies.
What is still missing is large-scale, prospective trial data testing whether gene-specific therapies actually improve survival in defined genetic subgroups of dilated cardiomyopathy, and funding to stratify patients by genotype in routine clinical settings. The 1994 data are now three decades old and reflect an era before widespread use of contemporary heart failure drugs. The mechanistic work on ΔK210 has not yet been translated into a clinical intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Heart · 1994 · 76 citations · open access
Changing mortality in dilated cardiomyopathy
AbstractOBJECTIVE: To analyse the changes in mortality in dilated cardiomyopathy over the past 15 years and to identify the factors that might have influenced survival. DESIGN: Follow up study of 235 patients (aged 16-70) systematically enrolled on a register from 1 January 1978 to 31 December 1992. SETTING: Hospital department of cardiology. PATIENTS: Three groups corresponding to three periods of 5 years: group 1 (diagnosis between 1 January 1978 and 31 December 1982) 26 patients; group 2 (diagnosis between 1 January 1983 and 31 December 1987) 65 patients; and group 3 (diagnosis between 1 January 1988 and 31 December 1992) 144 patients. MAIN OUTCOME MEASURES: Death or heart transplantation. RESULTS: Two and four year survival was 73.8% and 53.8% in group 1, 87.7% and 72.3% in group 2, and 90.3% and 82.9% in group 3 (P = 0.02). During the 15 years of the study period the number of cases increased progressively and the baseline clinical characteristics changed (that is, patients were younger and less severely affected), partly explaining the improvement in survival. None the less, the three mortality curves tended to diverge progressively and the improvement in survival in the different groups was still significant after stratification for the severity of the disease, suggesting that treatment had a sustained effect. A progressively higher proportion of patients were treated with angiotensin converting enzyme (ACE) inhibitors and more recently with beta blockers. In group 2, after stratification for the severity of heart failure, patients who were treated with ACE inhibitors showed a better survival than patients who were not. Furthermore, analysis of group 3 showed that beta blockers had a significant additive effect with conventional therapy both by intention to treat and actual treatment. Four year survival in patients with mild and moderate to severe heart failure treated with beta blockers, and usually digitalis and ACE inhibitors, was respectively 90% and 87.5%. CONCLUSIONS: The improvement in the survival of patients with dilated cardiomyopathy over the past 15 years may be explained by earlier diagnosis, new treatments, and a change in the clinical characteristics of the patients at enrolment.
Proceedings of the National Academy of Sciences · 2019 · 70 citations · open access
Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy
AbstractFamilial dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death and a major indicator for heart transplant. The disease is frequently caused by mutations of sarcomeric proteins; however, it is not well understood how these molecular mutations lead to alterations in cellular organization and contractility. To address this critical gap in our knowledge, we studied the molecular and cellular consequences of a DCM mutation in troponin-T, ΔK210. We determined the molecular mechanism of ΔK210 and used computational modeling to predict that the mutation should reduce the force per sarcomere. In mutant cardiomyocytes, we found that ΔK210 not only reduces contractility but also causes cellular hypertrophy and impairs cardiomyocytes' ability to adapt to changes in substrate stiffness (e.g., heart tissue fibrosis that occurs with aging and disease). These results help link the molecular and cellular phenotypes and implicate alterations in mechanosensing as an important factor in the development of DCM.
Annual Review of Medicine · 2023 · 64 citations · open access
Genetics of Dilated Cardiomyopathy
AbstractDilated cardiomyopathy (DCM) is defined as dilation and/or reduced function of one or both ventricles and remains a common disease worldwide. An estimated 40% of cases of familial DCM have an identifiable genetic cause. Accordingly, there is a fast-growing interest in the field of molecular genetics as it pertains to DCM. Many gene mutations have been identified that contribute to phenotypically significant cardiomyopathy. DCM genes can affect a variety of cardiomyocyte functions, and particular genes whose function affects the cell-cell junction and cytoskeleton are associated with increased risk of arrhythmias and sudden cardiac death. Through advancements in next-generation sequencing and cardiac imaging, identification of genetic DCM has improved over the past couple decades, and precision medicine is now at the forefront of treatment for these patients and their families. In addition to standard treatment of heart failure and prevention of arrhythmias and sudden cardiac death, patients with genetic cardiomyopathy stand to benefit from gene mechanism-specific therapies.
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.
