DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for thoracic aortic aneurysm — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThoracic aortic aneurysm maps to a 45-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 thoracic aortic aneurysm 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
methionine adenosyltransferase 2A (MAT2A) — MAT2A 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 samdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7RWG · 0.97 Å · ligand S-ADENOSYLMETHIONINE (SAM). Experimental structure, not a prediction.
What the evidence adds up to
In a 1999 study of 85 patients who received endovascular stent-grafts for descending thoracic aortic aneurysm, CT scans within 10 days of placement showed increased pleural effusion in 73% of 63 patients, periaortic changes in 33%, perigraft leak in 21%, atelectasis in 10%, mural thrombus within the stent-graft in 3%, and new aortic dissection in 2%. The mean maximum aneurysm diameter was 58.8 mm before and 60.0 mm after insertion. 98% of patients were successfully treated until discharge; 10 patients required interventional procedures to stop leakage into the aneurysm sac. The study concluded that thoracic CT is useful for managing these patients after stent-graft placement.
A 2020 review notes that thoracic aortic aneurysms and dissections are more commonly associated with an underlying genetic cause than abdominal aneurysms. Despite advances in genome sequencing that have identified several heritable aortopathies and provided insights into molecular mechanisms, there are limited consensus recommendations for clinical management. A 2011 review describes ascending aortic aneurysms as frequently linked to connective tissue diseases such as Marfan syndrome, a disorder of fibrillin-1. In mouse models with hypomorphic fibrillin-1 mutations, aortic dilations involve macrophage infiltration, elastin fragmentation, and enhanced TGF signalling. These aneurysms could be prevented by anti-TGF antibodies or the angiotensin II type 1 receptor antagonist losartan. Chronic infusion of angiotensin II into apoE-deficient mice is an established experimental model for inducing aortic aneurysms.
A 2023 review states that aortic aneurysms can affect any segment of the aorta, with abdominal aneurysms being more frequent than thoracic ones, and that these are distinct pathologies despite some similarities. The review notes that for a long time aortic wall aneurysms may evolve asymptomatically, but progressive dilatation can lead to aortic rupture. It states that there are limited therapies that may delay or prevent acute aortic syndromes, so surgical management remains the most common treatment. Although surgical techniques have become less invasive, the associated morbidity and mortality remain increased. The review calls for future studies comparing findings in human tissue and animal models so that clinically relevant conclusions about aneurysm formation and pharmacological blockage of pathogenic pathways can be drawn.
What is still missing are large-scale, randomised clinical trials testing specific pharmacological interventions in patients with thoracic aortic aneurysm, particularly those targeting TGF signalling or angiotensin II pathways. The existing evidence comes mostly from animal models and retrospective imaging studies, with no consensus on patient stratification by genetic subtype or aneurysm location. Funding for such trials and for translational work that bridges animal findings to human tissue remains inadequate.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractPURPOSE: To evaluate the usefulness of thoracic computed tomography (CT) after placement of an endovascular stent-graft for the treatment of descending thoracic aortic aneurysm. MATERIALS AND METHODS: From 1992 to 1996, 85 patients with thoracic aortic aneurysm underwent stent-graft placement. In 63 patients, thoracic CT scans were obtained both before and within 10 days after placement. The CT findings were retrospectively studied, and their clinical effect analyzed. In 20 of 63 patients, long-term follow-up CT findings were also evaluated. RESULTS: After stent-graft placement in the 63 patients, CT demonstrated an increase in pleural effusion in 46 (73%), periaortic changes in 21 (33%), perigraft leak in 13 (21%), atelectasis in six (10%), mural thrombus within the stent-graft in two (3%), and new aortic dissection in one (2%). The mean maximum diameter of the aneurysm was 58.8 mm before and 60.0 mm after stent-graft insertion. Sixty-two (98%) patients were successfully treated until discharge. Interventional procedures were performed to eliminate the leakage into the aneurysm sac in 10 patients with perigraft flow depicted at CT. Other complications were managed conservatively. CONCLUSION: Thoracic CT is useful in the treatment of patients after stent-graft insertion for the management of descending thoracic aortic aneurysm.
Vascular Medicine · 2020 · 28 citations · open access
Diagnostic approach and management of genetic aortopathies
AbstractAortic aneurysms were the primary cause of nearly 10,000 deaths in 2014 according to data from the Centers for Disease Control and may involve segments of the thoracic or abdominal aorta. Thoracic aortic aneurysms and dissections are more commonly associated with an underlying genetic etiology. In the past several decades, in parallel with the burst of new genome sequencing technologies, a number of genetic aortopathies have been identified. These have provided important insights into the molecular mechanisms of aneurysmal disease, but pose challenges in clinical practice as there are limited consensus recommendations at this time. In this review, we aim to address the pathophysiology, clinical presentation, and treatment considerations in the key heritable thoracic aortopathies.
Circulation Research · 2011 · 21 citations · open access
Parsing Aortic Aneurysms
AbstractA ortic aneurysms are progressive enlargements of the aorta that can lead to life-threatening degenerative changes in the structure of the artery wall including medial dissections and wall rupture. The abdominal aorta is the most common site of aneurysm formation, yet the ascending thoracic aorta can also exhibit aneurysmal expansion with potentially dire outcomes. Ascending aortic aneurysms are frequently associated with connective tissue diseases such as Marfan's syndrome, a disorder of the extracellular matrix protein fibrillin-1. 1 Mouse models carrying hypomorphic mutations in fibrillin-1 also develop aortic dilations associated with macrophage infiltration, elastin fragmentation, and enhanced transforming growth factor (TGF) signaling in the artery wall. 2 Aortic aneurysms in fibrillin-1 hypomorphic mice can be prevented by treatment with either anti-TGF neutralizing antibodies or with the angiotensin II (Ang II) type 1 (AT 1 ) receptor antagonist losartan. 3 Indeed, chronic infusion of Ang II into apoE / mice is an effective experimental model to induce aortic aneurysm formation and to study the molecular pathways underlying its pathogenesis.
Molecular and Cellular Mechanisms Involved in Aortic Wall Aneurysm Development
AbstractAortic aneurysms represent a very common pathology that can affect any segment of the aorta. These types of aneurysms can be localized on the thoracic segment or on the abdominal portion, with the latter being more frequent. Though there are similarities between thoracic and abdominal aortic aneurysms, these pathologies are distinct entities. In this article, we undertook a review regarding the different mechanisms that can lead to the development of aortic aneurysm, and we tried to identify the different manners of treatment. For a long time, aortic wall aneurysms may evolve in an asymptomatic manner, but this progressive dilatation of the aneurysm can lead to a potentially fatal complication consisting in aortic rupture. Because there are limited therapies that may delay or prevent the development of acute aortic syndromes, surgical management remains the most common manner of treatment. Even though, surgical management has improved much in the last years, thus becoming less invasive and sophisticated, the morbi-mortality linked to these therapies remains increased. The identification of the cellular and molecular networks triggering the formation of aneurysm would permit the discovery of modern therapeutic targets. Molecular and cellular mechanisms are gaining a bigger importance in the complex pathogenesis of aortic aneurysms. Future studies must be developed to compare the findings seen in human tissue and animal models of aortic aneurysm, so that clinically relevant conclusions about the aortic aneurysm formation and the pharmacological possibility of pathogenic pathways blockage can be drawn.
Journal of Visualized Surgery · 2018 · 0 citations · open access
Innovations in Thoracic Aortic Aneurysm Surgery
AbstractThis Special issue guest edited jointly by Dr. Mohamad Bashir and Dr. Joseph E. Bavaria aims to highlight clinical controversies and uncertainties regarding thoracic aortic aneurysm, its surgical treatment and innovations. The issue cross fertilised topics from a pool of international repute and brought them to clinical, scientific and academic platform to portray their Viewpoints, results and experiences. The emphasis of current aortic practice is centred around multi-disciplinary approach and linkage of thoughts, research and experiences. The issue dwelled on all concepts above reflecting on the future trends and projections in aortic surgery. We understand the ongoing need for new treatment options to provide effective and corrective surgery and such needs to be centred on foundations and pillars of extensive research and clinical expertise.
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.
