DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for heart valve disease — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHeart valve disease maps to a 31-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 heart 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
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
More than five million Americans have heart valve disease, a condition that no medication can cure; surgical intervention remains the only option at late stages. In a 2019 three-dimensional hydrogel model that incorporated mechanical stretching, valve interstitial cells treated with fibroblast growth factor 1 and 2 (FGF1 and FGF2) maintained a quiescent phenotype. Under pathological 20% cyclic stretch, FGF1 and FGF2 signalling via the FGFR1 receptor reduced cell proliferation and activation, which the authors suggested might represent a possible therapeutic strategy for preventing disease progression. The study was conducted entirely in vitro, and no human or animal treatment data were reported.
A 2001 review stated that drug therapy plays a key role in managing valvular heart disease but in many cases does not alter its course or delay the need for surgery. Drug therapy was described as important for stabilising patients with structural valve abnormalities and for treating underlying functional conditions, as well as for lowering the risk of bacterial endocarditis and rheumatic fever. No specific drug was shown to reverse or halt valve degeneration.
Heart valve disease prevalence is expected to double by 2040 and triple by 2060 due to population ageing, according to a 2021 policy review. The same review noted that effective treatment options exist and that early detection and treatment can dramatically change disease progression and reduce mortality, but that many patients are still diagnosed too late. A 2024 review emphasised an important genetic component in mitral valve prolapse and bicuspid aortic valve, both syndromic and non-syndromic, and stated that identifying new genes and molecular pathways is crucial for developing novel therapeutic strategies.
What is still missing are clinical trials testing FGF1 or FGF2 or FGFR1-targeting agents in patients with heart valve disease, funding for such translational work, and a clear stratification of patients by genetic subtype or valve lesion type that might predict response. No drug has yet been shown in a controlled human study to alter the natural history of heart valve disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Biological Engineering · 2019 · 22 citations · open access
The role of fibroblast growth factor 1 and 2 on the pathological behavior of valve interstitial cells in a three-dimensional mechanically-conditioned model
AbstractBACKGROUND: More than five million Americans suffer from heart valve disease annually, a condition that worsens cardiac function and gradually leads to heart failure if appropriate treatment is not performed on time. Currently no medication can cure heart valve disease, leaving surgical intervention as the only viable option for patients at late stages of cardiac valve disease. Tremendous efforts have been undertaken to elucidate how resident cells in the valves respond to pathological stimulation as well as the underlying mechanisms that regulate these responses, to identify potential therapeutic targets for non-surgical treatment of valvular heart disease. RESULTS: As a result, most cell signaling studies in the field have traditionally been conducted on two-dimensional models or in the absence of hemodynamic forces. Previously, we reported the fabrication of a hydrogel scaffold that could be used to culture valve cells under dynamic mechanical stimulation in a valve-mimetic environment. This model, therefore appeared to be suitable for VIC signaling studies as it provided cells a three-dimensional environment with the ability to incorporate mechanical stretching stimulation. Utilizing this model, we investigated the possible role of fibroblast growth factor 1 and 2 (FGF1 and FGF2) via FGFR1 receptor signaling in regulating valve cell activation under physiological (10% stretch) and pathological (20% stretch) mechanical conditions as well as in mediating cell proliferation and metabolism via the Akt/mTOR pathways. We reported that 1) FGF1 and FGF2 treatment was able to maintain the quiescent phenotype of VICs; 2) Cells increased proliferation as determined by optical redox ratios under elevated cyclic stretch via Akt/mTOR pathways; and 3) FGF1 and 2 signaling via the FGFR1 reduced VIC proliferation and activation under elevated cyclic stretch conditions. CONCLUSIONS: Overall, these results suggested that targeting FGFR1 receptor signaling may represent a possible therapeutic strategy for preventing heart valve disease progression.
European Heart Journal Open · 2021 · 18 citations · open access
Creating a better journey of care for patients with heart valve disease
AbstractHeart valve disease has been described as 'the next cardiac epidemic', with prevalence expected to double by 2040 and triple by 2060 due to the ageing of the population. Yet until now, it has been characterized by scarce data, limited research, and low general awareness compared with other cardiovascular diseases. Effective treatment options exist for heart valve disease, and early detection and treatment can dramatically change disease progression, improve quality of life, and reduce mortality. Unfortunately, in too many patients, heart valve disease is undetected, undiagnosed, untreated, or treated too late, leading to avoidable deaths and costs, and significant compromises to people's quality of life. These gaps in the patient pathway can be remedied through appropriate policy action, with a focus on: early detection and diagnosis; timely intervention; patient-centred follow-up care; patient engagement and empowerment; psychological support; and better data to guide practice. Ensuring all patients have access to appropriate diagnosis and care without delays is imperative as we look towards rebuilding stronger and more resilient health systems, and 'build back better' after the coronavirus disease-19 pandemic.
Cleveland Clinic Journal of Medicine · 2001 · 5 citations
Current medical management of valvular heart disease.
AbstractDrug therapy plays a key role in the management of valvular heart disease, though in many cases it does not alter its course or delay the need for surgery. The importance of drug therapy lies in stabilizing the patient's condition when the disease is due to abnormal valve structure, and in treating the underlying condition when the condition is due to a functional abnormality. Drug therapy also lowers the risk of bacterial endocarditis and rheumatic fever.
Reviews in Cardiovascular Medicine · 2024 · 4 citations · open access
Valvulopathies and Genetics: Where are We?
AbstractValvulopathies are among the most common cardiovascular diseases, significantly increasing morbidity and mortality. While many valvular heart diseases are acquired later in life, an important genetic component has been described, particularly in mitral valve prolapse and bicuspid aortic valve. These conditions can arise secondary to genetic syndromes such as Marfan disease (associated with mitral valve prolapse) or Turner syndrome (linked to the bicuspid aortic valve) or may manifest in a non-syndromic form. When cardiac valve disease is the primary cause, it can appear in a familial clustering or sporadically, with a clear genetic component. The identification of new genes, regulatory elements, post-transcriptional modifications, and molecular pathways is crucial to identify at-risk familial carriers and for developing novel therapeutic strategies. In the present review we will discuss the numerous genetic contributors of heart valve diseases.
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.
