DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for aortic disease — screening already-approved drugs against its 30-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAortic disease maps to a 30-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 aortic disease 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
serine/threonine kinase 25 (STK25) — STK25 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 5-~{tert}-butyl-1~{h}-pyrazol-3-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7Z4V · 1.644 Å · ligand ~{N}-(5-~{tert}-butyl-1~{H}-pyrazol-3-yl)-4-pyrrolidin-1-ylsulfonyl-benzamide (IB5). Experimental structure, not a prediction.
What the evidence adds up to
In a 2013 review of genetic aneurysm syndromes, the proportion of thoracic and abdominal aortic aneurysms and dissections attributable to a genetic predisposition remains unknown, and the causative genes and molecular pathways involved in aortic aneurysm disease are still undiscovered. A 2019 review notes that the number of newly identified genetic causes for aortopathies has continued to increase over the past 10 years, but the number of reported individuals with most hereditary aneurysm genes is small. Advances in genetic testing technology have increased the importance of molecular diagnostics in evaluating and managing hereditary aortic disease, and molecular diagnostics and family phenotyping can aid in the diagnosis and management of paediatric patients.
A 2020 single-centre cohort study of 105 consecutive patients with acute Stanford type B aortic dissection applied selection criteria of age of disease onset ≤45 years or a positive family history for aortic disease. Only nine patients met these criteria and underwent next-generation sequencing for a panel of 30 genes associated with familial thoracic aortic aneurysm and dissection syndrome. Causal variants were found in four patients: three carried pathogenic variants in FBN1 (fibrillin-1), and a fourth carried a large copy number variant deleting eleven genes on chromosome 10, including the entire ACTA2 gene. Two of these genetic findings had not been reported before. The study concludes that selecting patients based on young age and familial inheritance favours identification of disease-causing genetic variants, but the sample of patients who qualified for testing was small.
A 2023 review of medical management for aortic disease states that surgery remains the cornerstone of management for most aortic conditions, and that medical therapy is now an important adjunctive therapy in most if not all patients. The review does not report any specific drug, survival, or response rate data. What is still missing are large, unselected cohorts that can establish the true prevalence of genetic causes in aortic disease, prospective trials that test whether genetic findings alter surgical or medical outcomes, and funding to support the multidisciplinary teams and long-term follow-up needed to move from genetic discovery to clinical benefit.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Vascular Medicine · 2013 · 109 citations · open access
Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections
AbstractThere are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD). In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.
Journal of Thoracic Disease · 2020 · 13 citations · open access
Acute Stanford type B aortic dissection—who benefits from genetic testing?
AbstractBackground: Stanford type B aortic dissection is a rare, life-threatening complex phenotype associated with several modifiable and genetic risk factors. In the current study of a hospital-based, consecutive series of aortic dissection patients we propose a selection based on age and family history of aortic disease for genetic testing and detection of causative gene variants. Methods: In this single center cohort study from 2013 to 2018 patients with acute Stanford type B aortic dissections were consecutively treated and analyzed by next generation sequencing based on selection criteria (age of disease onset ≤45 years and/or positive familial history for aortic disease) to detect genome-wide pathogenic variants in protein-coding sequences and to identify large copy number variants (CNV). Variants in a predefined panel of 30 genes associated with the familial thoracic aortic aneurysm and dissection (TAAD) syndrome were evaluated. Results: From 105 patients nine matched selection criteria for genetic testing. Next-generation sequencing analysis revealed causal variants in FBN1 (fibrillin-1) in three patients: a pathogenic missense variant [c.6661T>C, p.(Cys2221Arg)] and two truncating variants [c.4786C>T, p.(Arg1596Ter)] and [c.6366C>CA, p.(Asp2123GlufsTer5)]. A fourth patient carried a large (>1,000,000 bp) CNV in the long arm of chromosome 10, deleting eleven genes, including the whole ACTA2 (actin alpha 2) gene. The latter two genetic findings have not been reported before. Conclusions: Selection of patients on the basis of young age and familial inheritance of aortic disease favors the identification of disease-causing genetic variants in a clinical cohort of patients with Stanford type B aortic dissection.
Current Opinion in Pediatrics · 2019 · 10 citations
Genetics of syndromic and nonsyndromic aortopathies
AbstractPURPOSE OF REVIEW: To review the literature and provide a summary of management of syndromic and nonsyndromic aortopathies. RECENT FINDINGS: The number of newly identified genetic causes for aortopathies have continued to increase over the past 10 years. The number of reported individuals with most hereditary aneurysm genes is small but increasing with more publications focusing describing the natural history caused by each gene. SUMMARY: Aortopathy can present as an isolated finding or present as part of a larger genetic syndrome. Advances in genetic testing technology has shed light on the increasing importance of molecular diagnostics in the evaluation and management of patients with hereditary aortic disease. Molecular diagnostics and family phenotyping can aide in the diagnosis and management of pediatric patients with aortic disease.
Medical Management of Aortic Disease: If They Don’t Need Surgery, What Do They Need?
AbstractManagement of aortic disease has evolved significantly over the past few decades. A preemptive diagnostic approach with a multidisciplinary team and shared decision-making has led to improved clinical outcomes. Surgery is the cornerstone of management for most aortic conditions; however, medical therapy is now an important adjunctive therapy in most if not all patients. Herein, we review the role and evidence behind medical management of patients with aortic disease.
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.
