DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for aortic stenosis — screening already-approved drugs against its 66-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAortic stenosis maps to a 66-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 stenosis 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
lipoprotein(a) (LPA) — LPA 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8TCE · 1.07 Å · ligand (2S)-3-phenyl-2-[(3R)-pyrrolidin-3-yl]propanoic acid (HWF). Experimental structure, not a prediction.
What the evidence adds up to
Untreated severe symptomatic aortic stenosis carries a dismal prognosis, and aortic valve replacement remains the only treatment shown to improve survival. Multiple systematic reviews and overviews from 2011 through 2023 confirm that no pharmacological therapy has yet been shown to slow or halt progression of the disease. Lipid-lowering drugs, antihypertensives, and anticalcific agents have been studied, but clinical evidence for efficacy is lacking. The 2023 review states plainly that despite promising observational data, pharmacological management to slow or halt progression has remained elusive.
In a 2016 mouse model, hypercholesterolemic/hypertensive Apoe(-/-) mice developed severe aortic stenosis with minimal calcification, instead showing fibrotic changes at the valve base: lengthening of the intercusp raphe, reorientation of collagen fibres, and asymmetrical cusps. Plasminogen activator inhibitor 1, a profibrotic molecule, was greatly increased at both RNA and protein levels. This model resembles aortic stenosis in children and some adults, but no drug intervention was tested in that study.
Biomarker research has identified lipoprotein(a) as the most promising marker for risk stratification; elevated Lp(a) is associated with more rapid progression, attributed to promotion of valve calcification. Other emerging biomarkers such as matrix metalloproteinases, monocytes, and metabolites are noted but their roles remain unclear. Genetic markers are also under investigation, but none has yet translated into a therapeutic target that changes clinical outcomes.
What is still missing is a completed, adequately powered randomised trial of any drug that shows a reduction in valve progression or need for valve replacement. The preclinical models have not yet produced a candidate that has succeeded in human trials. Patient stratification by Lp(a) level or genetic profile remains aspirational. Funding for such trials, and trial designs that account for the slow natural history of the disease, are the practical barriers.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Circulation · 2016 · 158 citations
Medical Treatment of Aortic Stenosis
AbstractUntreated, severe, symptomatic aortic stenosis is associated with a dismal prognosis. The only treatment shown to improve survival is aortic valve replacement; however, before symptoms occur, aortic stenosis is preceded by a silent, latent phase characterized by a slow progression at the molecular, cellular, and tissue levels. In theory, specific medical therapy should halt aortic stenosis progression, reduce its hemodynamic repercussions on left ventricular function and remodeling, and improve clinical outcomes. In the present report, we performed a systematic review of studies focusing on the medical treatment of patients with aortic stenosis. Lipid-lowering therapy, antihypertensive drugs, and anticalcific therapy have been the main drug classes studied in this setting and are reviewed in depth. A critical appraisal of the preclinical and clinical evidence is provided, and future research avenues are presented.
Clinical Cardiology · 2018 · 70 citations · open access
Subvalvular aortic stenosis: a review of current literature
AbstractSubvalvular aortic stenosis (SAS) is one of the common adult congenital heart diseases, with a prevalence of 6.5%. It is usually diagnosed in the first decade of life. Echocardiography is the test of choice to diagnose SAS. Surgical correction is the best treatment modality, and the prognosis is usually excellent. In this review, we describe the pathophysiology, diagnosis, prognosis, and management of SAS with a focus on different pathophysiologic mechanisms, diagnostic approach, and prognosis of the disease by reviewing the current literature.
Arteriosclerosis Thrombosis and Vascular Biology · 2016 · 28 citations · open access
Fibrotic Aortic Valve Stenosis in Hypercholesterolemic/Hypertensive Mice
AbstractOBJECTIVE: Hypercholesterolemia and hypertension are associated with aortic valve stenosis (AVS) in humans. We have examined aortic valve function, structure, and gene expression in hypercholesterolemic/hypertensive mice. APPROACH AND RESULTS: Control, hypertensive, hypercholesterolemic (Apoe(-/-)), and hypercholesterolemic/hypertensive mice were studied. Severe aortic stenosis (echocardiography) occurred only in hypercholesterolemic/hypertensive mice. There was minimal calcification of the aortic valve. Several structural changes were identified at the base of the valve. The intercusp raphe (or seam between leaflets) was longer in hypercholesterolemic/hypertensive mice than in other mice, and collagen fibers at the base of the leaflets were reoriented to form a mesh. In hypercholesterolemic/hypertensive mice, the cusps were asymmetrical, which may contribute to changes that produce AVS. RNA sequencing was used to identify molecular targets during the developmental phase of stenosis. Genes related to the structure of the valve were identified, which differentially expressed before fibrotic AVS developed. Both RNA and protein of a profibrotic molecule, plasminogen activator inhibitor 1, were increased greatly in hypercholesterolemic/hypertensive mice. CONCLUSIONS: Hypercholesterolemic/hypertensive mice are the first model of fibrotic AVS. Hypercholesterolemic/hypertensive mice develop severe AVS in the absence of significant calcification, a feature that resembles AVS in children and some adults. Structural changes at the base of the valve leaflets include lengthening of the raphe, remodeling of collagen, and asymmetry of the leaflets. Genes were identified that may contribute to the development of fibrotic AVS.
Medical Therapy to Prevent or Slow Progression of Aortic Stenosis: Current Evidence and Future Directions
AbstractDegenerative aortic stenosis is a growing clinical problem owing to the high incidence in an aging population and its significant morbidity and mortality. Currently, aortic valve replacement remains the only treatment. Despite promising observational data, pharmacological management to slow or halt progression of aortic stenosis has remained elusive. Nevertheless, with a greater understanding of the mechanisms which underpin aortic stenosis, research has begun to explore novel treatment strategies. This review will explore the historical agents used to manage aortic stenosis and the emerging agents that are currently under investigation.
Current Opinion in Cardiology · 2019 · 7 citations
Predicting the future of TAVR
AbstractPURPOSE OF REVIEW: Transcatheter aortic valve replacement (TAVR) has become the cornerstone for aortic valve intervention since the first implantation in 2002. Recent advances with novel devices and introduction into lower risk cohorts have been successful. In this review, we discuss the ongoing limitations to transcatheter aortic valve therapy and whether it will replace surgical aortic valve replacement in the foreseeable future. RECENT FINDINGS: A better understanding of valve durability, high-grade heart block, and stroke post TAVR has led to practice changes that improve patient outcome. SUMMARY: Although there has been great progress made in treating severe aortic stenosis with TAVR, there are room for improvements before it becomes the default therapy for all patients.
International Journal of Molecular Sciences · 2025 · 4 citations · open access
Novel Circulating Biomarkers in Aortic Valve Stenosis
AbstractThe underlying pathophysiology of aortic stenosis and factors affecting its clinical progression remain poorly understood. Apart from B-type natriuretic peptide (BNP), novel and emerging biomarkers have been described in association with aortic stenosis, emphasising the potential for these biomarkers to illuminate on yet unknown mechanisms of its pathogenesis. In this review, we aimed to summarise what is known about aortic stenosis biomarkers, highlight the emerging ones, and provide a roadmap for translating these insights into clinical applications. Among the biomarkers studied, lipoprotein(a) [Lp(a)] has emerged as the most promising for risk stratification. Elevated Lp(a) levels are often associated with more rapid aortic stenosis progression. This detrimental effect is attributed to its role in promoting valve calcification. While other emerging biomarkers such as matrix metalloproteinases, monocytes, and metabolites show promises, their specific roles in aortic stenosis pathophysiology remain less clear. This may be due to their relatively recent discovery. Ongoing research aims to elucidate their mechanisms of action.
Russian Journal of Cardiology · 2015 · 1 citations · open access
MOLECULAR-GENETIC FACTORS, ASSOCIATED WITH AORTIC STENOSIS DEVELOPMENT
AbstractAortic stenosis (AS) is one of the most prevalent valvular heart disorders in patients older than 65 years. Regardless the studied molecular mechanisms of development and progression of the disease, surgical treatment is recently the only successful method of help. Due to lots of comorbidities of older patients, there are obstacles to recommend surgical valve replacement, even knowing an adverse prognosis of conservative treatment. Search for new approaches to earlier assessment of adverse risk factors, speed of progression of this disease, would help to evaluate the necessity of earlier treatment and could make to slow down the progression of the disease. One of directions for this — is a search for genetic markers. This review focuses on the main known molecular mechanisms and genetic markers related to them, that are associated with AS.
Trends in Degenerative Aortic Disease: Novel Alternative Therapies for the Treatment of Severe Aortic Stenosis
AbstractAortic stenosis is the most common valvular disease among the occidental population and it is one of the most important causes of morbidity and mortality in developed countries. It has an incidence of 4% among over 80 years old patients Its evolution is generally slowly progressive from asymptomatic/mild aortic stenosis to the symptomatic/severe form when survival is dramatically reduced as well as quality of live is importantly impaired. Occasionally in-hospital admittance will be unavoidable and this will necessarily arise into economic resources consumption, that might be assumed by actually over-the-edge and almost bankrupted socio-sanitary policies, at least in the most of developed countries (Varadarajan P, 2006; Pai RG, 2006). Over more tan 40 years, standard treatment for severe symptomatic aortic stenosis has been focused in surgical replacement of the affected valve for a mechanical prosthesis. To achieve this replacement, patient must mandatorily undergo several risky procedures as general anesthesia, median sternotomy, and aortic arch clamping and cardioplegic solution infusion in order to maintain cardiac arrest in diastole during the intervention, with the indispensable cardiopulmonary bypass pumping. These patients must then admit the natural history of this disease with a terribly poor mid-term prognosis and elevated economic expenses for the system. In this moment, several therapeutic alternatives are being studied with the aim of the risk reduction in the management of patients with severe aortic stenosis and surgical high-risk profile. These therapies do not pretend to become a substitution of the standard surgical www.intechopen.com Aortic Valve Stenosis -Current View on Diagnostics and Treatment 130 therapy but a way to reduce the burden of complication and morbidity in the subgroup of patients that cannot be eligible for standard surgery. Special surgical new techniques as low-profile mechanical prosthesis, biological prosthesis (both stented and stentless), homograft and Ross technique (pulmonary autograft in aortic position and homograft in pulmonary position) will not be commented in this chapter.
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.
