DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for tricuspid valve disease — screening already-approved drugs against its 28-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTricuspid valve disease maps to a 28-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 tricuspid valve 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
phosphodiesterase 4D (PDE4D) — PDE4D 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 difluoromethoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5WH6 · 1.6 Å · ligand 1-[4-(difluoromethoxy)-3-{[(3S)-oxolan-3-yl]oxy}phenyl]-3-methylbutan-1-one (AKJ). Experimental structure, not a prediction.
What the evidence adds up to
Tricuspid valve disease has historically received less attention than left-sided valve disease, but recent data show that tricuspid regurgitation is not benign and that many patients benefit from intervention. Over 90% of stenotic tricuspid valves are caused by rheumatic disease; isolated tricuspid stenosis is either carcinoid or congenital, with rare causes including active infective endocarditis, Fabry’s disease, Whipple’s disease, and giant blood cysts. Isolated tricuspid valve surgery remains rare and continues to carry the highest surgical risk among all valve procedures, with high operative mortality especially in reoperations. Functional non-organic tricuspid regurgitation is clinically of primary importance.
Latest valve guidelines now recommend a more aggressive surgical approach to moderate or severe tricuspid regurgitation, with annuloplasty as the preferred technique, and also promote prophylactic treatment of isolated significant tricuspid dilatation even without significant regurgitation. For high-risk surgical patients, transcatheter therapies are emerging as an alternative. Multiple percutaneous therapies have been developed for severe tricuspid disease, initially repair and more recently replacement. The valve-in-valve procedure for the tricuspid valve is reported as feasible and safe across all sizes of presentation, without the untoward risks of conventional surgery. Various repair devices have reported early experience.
In nonsyndromic tricuspid atresia, the third most common cyanotic congenital heart defect, screening of 40 individuals for mutations in ZFPM2/FOG2 and HEY2 genes found no pathogenetic mutation, failing to demonstrate a major role for these genes in human tricuspid atresia. The genetic mechanism responsible for tricuspid atresia remains obscure.
What is still missing are large randomised trials comparing transcatheter interventions to medical therapy or surgery in specific patient subgroups, standardised definitions of tricuspid regurgitation severity and right ventricular function to guide patient selection, and dedicated funding for device development and long-term outcome registries. The underlying molecular pathways driving isolated tricuspid valve disease, beyond rheumatic and carcinoid causes, remain largely unknown.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Cardiology · 1995 · 63 citations
Pathology of tricuspid valve stenosis and pure tricuspid regurgitation—Part I
AbstractThis three-part article examines the histologic and morphologic basis for stenotic and purely regurgitant tricuspid valves. In Part I, conditions producing tricuspid valve stenosis are reviewed. In over 90% of stenotic tricuspid valves, the etiology is rheumatic disease. In isolated tricuspid stenosis, the etiology is either carcinoid or congenital. Rare causes of tricuspid stenosis include active infective endocarditis, metabolic or enzymatic abnormalities (Fabry's, Whipple's disease), and giant blood cysts.
Frontiers in Cardiovascular Medicine · 2018 · 47 citations · open access
Surgical Techniques for Tricuspid Valve Disease
AbstractTricuspid valve disease affects millions of patients worldwide. It has always been considered less relevant than the left-side valves of the heart, but this "forgotten valve" still represents a great challenge for the cardiac surgeons, especially in the most difficult symptomatic scenarios. In this review we analyze the wide spectrum of surgical techniques for the treatment of a diseased tricuspid valve.
American Journal of Medical Genetics Part A · 2005 · 23 citations
ZFPM2/FOG2 andHEY2 genes analysis in nonsyndromic tricuspid atresia
AbstractTricuspid atresia (TriAt), the third most common cyanotic congenital heart defect (CHD), consists of complete lack of tricuspid valve formation, with no connection between the right atrium and the right ventricle. To date, the genetic mechanism responsible of TriAt is still obscure. However, animal models have suggested a role of cardiogenic Zfpm2/Fog2 and Hey2 genes in the pathogenesis of TriAt. Therefore, we screened 40 individuals affected by nonsyndromic TriAt for ZFPM2/FOG2 and HEY2 gene mutations. No pathogenetic mutation has been identified, thus failing to demonstrate a major role of ZFPM2/FOG2 and HEY2 genes in the pathogenesis of human TriAt.
Current Opinion in Cardiology · 2017 · 15 citations
Innovations in tricuspid valve intervention
AbstractPURPOSE OF REVIEW: Tricuspid valve disease has received much less attention in terms of intervention. The main reason for this is the widely held belief that treatment of left-sided valve disease leads to resolution of functional tricuspid regurgitation. Recent data show that tricuspid regurgitation is not benign and that many patients will benefit from intervention at the time of left-sided valve surgery, or in isolated tricuspid disease. This review describes the latest surgical and interventional options and strategies. RECENT FINDINGS: Latest valve guidelines now recommend a more aggressive surgical approach to the treatment of moderate or severe tricuspid regurgitation, with annuloplasty being the preferred technique. Guidelines now also promote treatment of isolated significant tricuspid dilatation even without significant regurgitation, as a prophylactic strategy to prevent disease progression. This renewed interest in surgical repair has been accompanied by development of newer tricuspid annuloplasty rings. For patients in whom surgery would be high risk, transcatheter therapies are emerging as a promising alternative. Various repair devices have reported early experience. SUMMARY: Recent surgical and transcatheter innovations in the treatment of tricuspid valve disease are promising and have the potential of removing the stigma of the tricuspid valve as the 'forgotten valve'.
Journal of Clinical Medicine · 2021 · 14 citations · open access
Transcatheter Tricuspid Valve-in-Valve Procedure—An Illustrative Case Report and Review
AbstractSevere tricuspid commitment is no longer understood as merely a marker of disease but is now widely thought of as a significant contributor to cardiac morbidity and mortality. However, isolated tricuspid valve surgery remains rare and to this day continues to be associated with the highest surgical risk among all valve procedures and high operative mortality rates, especially in reoperations. Therefore, the development of tricuspid transcatheter procedures is as necessary as it was for the other valves a couple of years ago. Recently, multiple percutaneous therapies have been developed for the management of severe tricuspid disease, initially only repair and more recently replacement, thus creating a new branch for the management of patients who have already undergone surgery and who present with dysfunctional bioprostheses. The purpose of this review and report is to demonstrate current and possible future challenges, and to show that the valve-in-valve procedure of the tricuspid valve is feasible and safe, and now can be performed in all its range, in the smallest to the largest sizes of presentation, without incurring the untoward risks of conventional surgery.
Isolated tricuspid valve disease in antiphospholipid syndrome
AbstractCardiac valve involvement in antiphospholipid syndrome (APS) has been consistently shown. However, isolated tricuspid valve disease within this syndrome has only been recently reported. We report a patient with primary antiphospholipid syndrome who had isolated tricuspid organic valve disease, pulmonary hypertension and pulmonary thromboembolism. We suggest that the APS should be listed as one of the aetiologies of organic isolated tricuspid valve disease in the adult population.
Giornale italiano di cardiologia · 2019 · 1 citations
Nuove possibilità terapeutiche nel trattamento dell’insufficienza tricuspidale
AbstractTricuspid regurgitation is a common finding in patients with left-sided heart disease with prognostic implications. In addition, isolated tricuspid valve surgery is associated with high mortality and is infrequently performed. Hence, a largely unmet clinical need exists and less invasive therapeutic options are emerging: multiple percutaneous therapies have been developed, including tricuspid valve repair or replacement. This review aims to provide an overview with diagnostic and clinical perspectives, potential challenges and future directions.
[Anatomy and pathology of the tricuspid valve (author's transl)].
AbstractAnatomy and pathology of the tricuspid valve are presented in a short survey. Annulus fibrosus and leaflets are less firm than those of the mitral valve, whereas the tricuspid orifice is larger than the mitral orifice. Isolated tricuspid disease - congenital or acquired - occurs only rarely. Functional non organic tricuspid regurgitation is clinically of primary importance.
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.
