DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for supravalvular 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 moduleSupravalvular 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 supravalvular 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.
What the evidence adds up to
Supravalvular aortic stenosis is caused by a loss-of-function mutation of the elastin gene on chromosome 7q11.23, resulting in an obstructive arteriopathy most prominent at the aortic sinutubular junction. The disease is generalised and frequently associated with stenoses of systemic and pulmonary arteries. The location of the narrowing at the level of the aortic valve commissures has implications for both aortic valve function and coronary circulation. These features, beyond the mere supra-aortic narrowing, have important implications for surgical therapy.
Two cases of supravalvular aortic stenosis occurring as an early complication after the arterial switch operation for transposition of the great arteries were treated with balloon angioplasty. Both patients showed improvement in post-angioplasty gradients and angiographic appearance. At short-term follow-up, both had persistent improved gradient and did not require further intervention. This is a rare complication, and transcatheter intervention is uncommon because surgical re-intervention has traditionally been performed.
A review of degenerative aortic stenosis notes that it is the most common valvular disease in the occidental population, with an incidence of 4% among people over 80 years old. Standard treatment for severe symptomatic aortic stenosis has been surgical valve replacement, which requires general anaesthesia, sternotomy, aortic arch clamping, cardioplegic arrest, and cardiopulmonary bypass. The review discusses alternative therapies aimed at reducing risk in patients with a high surgical profile, but it does not present data on any specific drug treatment for supravalvular aortic stenosis.
What is still missing is any randomised trial of a pharmacological therapy for supravalvular aortic stenosis, whether congenital or acquired. The evidence consists of case reports of balloon angioplasty in a handful of patients and a review of surgical alternatives for degenerative aortic stenosis that does not address the congenital form. No drug has been tested in a controlled fashion for this condition, and no patient stratification or funding for such a trial is reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Cardio-Thoracic Surgery · 2001 · 153 citations · open access
Congenital supravalvar aortic stenosis: a simple lesion?
AbstractThe underlying cause of congenital supravalvular aortic stenosis (SVAS) has recently been identified as a loss-of function mutation of the elastin gene on chromosome 7q11.23, resulting in an obstructive arteriopathy of varying severity, which is most prominent at the aortic sinutubular junction. The generalized nature of the disease explains the frequent association with stenoses of systemic and pulmonary arteries. Furthermore, localization of the supravalvular stenosis at the level of the commissures of the aortic valve has important implications for both aortic valve function and coronary circulation. This review summarizes the recent advances with regard to the pathogenesis of SVAS and describes the multitude of clinically relevant pathologic features other that the mere 'supra-aortic' narrowing that have important implications for surgical therapy.
Annals of Pediatric Cardiology · 2018 · 2 citations · open access
Balloon angioplasty for supravalvular aortic stenosis as an early complication following arterial switch operation
AbstractSupravalvular aortic stenosis as an early complication of transposition of the great artery repair is rare with few cases reported. Furthermore, transcatheter intervention is uncommon as surgical re-intervention has been traditionally done. We describe two cases of supravalvular aortic stenosis at the anastomotic site as an early complication of the arterial switch operation. Both patients underwent balloon angioplasty of the supravalvular aorta with improvement in postangioplasty gradients and angiographic appearance. Both patients at short-term follow-up had persistent improved gradient without need for further intervention.
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.
