DeCure for Ehlers-Danlos syndrome, cardiac valvular type
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for Ehlers-Danlos syndrome, cardiac valvular type — 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 moduleEhlers-Danlos syndrome, cardiac valvular type 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 ehlers-danlos syndrome, cardiac valvular type 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
collagen type I alpha 2 chain (COL1A2) — COL1A2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8YV3 · 1.68 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 1987 report, a form of Ehlers-Danlos syndrome with minimal external findings but severe internal vascular complications was described. The report did not provide sample sizes, survival rates, or response rates for any intervention.
A 2019 retrospective study at a single tertiary centre identified 262 patients with any form of Ehlers-Danlos syndrome. Echocardiography was performed in 90% of patients and cardiac evaluation in 50%. Cardiovascular complications occurred in 50% of patients with vascular Ehlers-Danlos syndrome, but echocardiography was normal in all of those patients. Aortic dilation was common in classic Ehlers-Danlos syndrome but absent in hypermobile Ehlers-Danlos syndrome. Mitral valve prolapse and bicuspid aortic valve occurred at the same incidence as the general population. Cardiac symptoms were present in 12% of patients but did not correlate with abnormal cardiac structure. Presentation with musculoskeletal pain was inversely related to the presence of cardiac pathology. The authors concluded that routine cardiac evaluation and echocardiography are not required for patients with hypermobile Ehlers-Danlos syndrome.
A 2024 study of 26 adults with genetically confirmed vascular Ehlers-Danlos syndrome (vEDS) and 26 matched healthy controls used cardiac MRI. Left and right ventricular ejection fractions were lower in vEDS compared with controls (LVEF 58 ± 6% vs 61 ± 4%, P = .03; RVEF 54 ± 5% vs 58 ± 4%, P = .03). After controlling for age, sex, and antihypertensive medication, LV end-diastolic volume indexed to body surface area predicted dissections (OR 1.1, 95% CI 1.01-1.2, P = .04) and aneurysms (OR 1.1, 95% CI 1.01-1.3, P = .03). Indexed LV end systolic volume also predicted aneurysms (OR 1.2, 95% CI 1.03-1.5, P = .02). LVEF predicted the presence of any complication (OR 0.71, 95% CI 0.52-0.99, P = .04). Among those with LVEF below the mean of 58%, pneumothorax occurred in 50.0% versus 0.0% in those with LVEF above the mean (P = .02). Those with LVEF below 58% had more frequent dissection or aneurysm (75.0% vs 12.5%, P = .04). No drug was tested in any of these studies. What is still missing is prospective data linking these imaging findings to a modifiable target, a trial design that tests whether intervening on ventricular size or function alters outcomes, and patient stratification that accounts for the genetic heterogeneity across EDS types.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 1987 · 20 citations
Cardiovascular complications in the Ehlers‐Danlos syndrome with minimal external findings
AbstractEhlers-Danlos syndrome (EDS) is clinically and genetically a heterogeneous disorder of connective tissue. Eleven different types of EDS have been documented, several of which have major cardiovascular complications as part of their clinical manifestations. The purpose of this report is to call attention to a form of EDS with minimal external features but severe internal vascular complications.
Utilization of echocardiography in Ehlers‐Danlos syndrome
AbstractOBJECTIVES: This study assessed the frequency and utility of echocardiographic examination in patients with all forms of Ehlers-Danlos syndrome and sought to identify clinical variables associated with an abnormal echocardiogram. DESIGN/SETTING: This was a retrospective study of all patients carrying a diagnosis of Ehlers-Danlos syndrome of any type who were evaluated by a pediatrician or pediatric subspecialist at a single tertiary medical center with an affiliated children's hospital during the period January 2013 to December 2018. PATIENTS: Chart review was performed on all patients carrying a diagnosis of Ehlers-Danlos syndrome in the electronic medical record. OUTCOME MEASURES: Data from genetics examination, cardiovascular examination where applicable, genetic test results when available, and echocardiography were recorded. RESULTS: Of 262 patients identified, echocardiography and cardiac evaluation were common occurring in 90% and 50% of patients with any form of Ehlers-Danlos syndrome. Cardiovascular complications occurred in 50% of patients with vascular Ehlers-Danlos syndrome but echocardiography was normal in all. Aortic dilation was common in classic Ehlers-Danlos syndrome but absent in hypermobile Ehlers-Danlos syndrome. Mitral valve prolapse and bicuspid aortic valve occurred at the same incidence as the general population. Cardiac symptoms were present in 12% but did not correlate with abnormal cardiac structure. Presentation with symptoms of musculoskeletal pain was inversely related to the presence of cardiac pathology. CONCLUSIONS: In light of the absence of cardiac pathology in patients with hypermobile Ehlers-Danlos syndrome, routine cardiac evaluation and echocardiography are not required for patients with hypermobile Ehlers-Danlos syndrome.
Canadian Association of Radiologists Journal · 2024 · 3 citations · open access
Association Between Cardiac Size, Systolic Function, and Complications in Vascular Ehlers-Danlos Syndrome
AbstractPurpose: Vascular Ehlers-Danlos syndrome (vEDS) is a rare and aggressive heritable aortic disease caused by pathogenic variants in COL3A1 gene, characterized by spontaneous arterial dissection and organ rupture. The purpose of this study is to evaluate ventricular size and function and to explore their associations with complications in vEDS. Methods: Adults with genetically confirmed vEDS who underwent clinical cardiac MRI were retrospectively compared with controls matched for age and sex. Cardiac MRI analysis included assessment of ventricular volumetry and arterial vasculature. vEDS-related complications were evaluated including dissection, aneurysm, and pneumothorax. Multivariable logistic regression was performed. Results: We studied 26 individuals with vEDS (38.6 ± 15.6 years, 50.0% female) and 26 healthy controls. Median clinical follow-up was 2.4 (1.1-3.6) years. Left and right ventricular ejection fractions were lower in vEDS compared with controls (LVEF 58 ± 6% vs 61 ± 4%, P = .03; RVEF 54 ± 5% vs 58 ± 4%, P = .03). After controlling for age, sex, and antihypertensive medication, LV end-diastolic volume indexed to body surface area (LVEDVi) predicted dissections (OR 1.1, 95% CI 1.01-1.2, P = .04) and aneurysms (OR 1.1, 95% CI 1.01-1.3, P = .03). Indexed LV end systolic volume (LVESVi) also predicted aneurysms (OR 1.2, 95% CI 1.03-1.5, P = .02). LVEF predicted the presence of any complication (OR 0.71, 95% CI 0.52-0.99, P = .04). Pneumothorax occurred exclusively in vEDS group among those with LVEF <58% (below the mean), 50.0% versus 0.0%, P = .02. Those with LVEF <58% had more frequent dissection and/or aneurysm (75.0% vs 12.5%, P = .04). Conclusion: Lower LVEF and larger cardiac size are associated with complications in vEDS.
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.
