DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for subvalvular aortic stenosis — 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 moduleSubvalvular aortic stenosis 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 subvalvular 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
desmoplakin (DSP) — DSP 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 4s,5sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3R6N · 2.95 Å · ligand (4S,5S)-1,2-DITHIANE-4,5-DIOL (D1D). Experimental structure, not a prediction.
What the evidence adds up to
No drug therapy has been shown to improve survival in severe symptomatic aortic stenosis; the only treatment that does is aortic valve replacement. A 2016 systematic review examined lipid-lowering therapy, antihypertensive drugs, and anticalcific therapy for aortic stenosis but provided no evidence that any of these drug classes halts progression or improves clinical outcomes in patients. The review did not report any positive trial results for drug treatment of the condition.
Subvalvular aortic stenosis is a distinct congenital form, with a prevalence of 6.5% and usually diagnosed in the first decade of life. A 2018 review states that surgical correction is the best treatment modality and that prognosis after surgery is usually excellent. No medical therapy is mentioned for subvalvular aortic stenosis in that review.
A 2008 review of low-gradient aortic stenosis notes that symptomatic patients who undergo valve replacement experience a vast reduction in symptoms and improved survival. It does not report any drug treatment that achieves similar results. A 2015 review of molecular and genetic factors in aortic stenosis concludes that surgical treatment remains the only successful method, and that conservative treatment carries an adverse prognosis.
What is still missing: no randomised trial has tested any drug specifically for subvalvular aortic stenosis; no drug has been shown to slow progression or reduce the need for surgery in this population; patient stratification by genetic or molecular markers remains hypothetical and untested in a clinical trial.
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.
Catheterization and Cardiovascular Interventions · 2008 · 3 citations
Low gradient aortic stenosis: Assessment, treatment, and outcome
AbstractAortic stenosis is a commonly encountered valvular disorder in the treatment of cardiovascular disease. Generally, symptomatic patients who undergo valve replacement experience a vast reduction in symptoms and a great improvement in survival. A subset of symptomatic patients in whom management is less clear are those with a small transvalvular gradient and low cardiac output, or low gradient aortic stenosis. The assessment, treatment, and outcome of this unique group of patients will be reviewed.
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.
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.
