DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intermittent vascular claudication — screening already-approved drugs against its 43-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIntermittent vascular claudication maps to a 43-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 intermittent vascular claudication 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 6D (PDE6D) — PDE6D 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 6rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4JV8 · 1.45 Å · ligand (6R)-6-(pyridin-2-yl)-5,6-dihydrobenzimidazo[1,2-c]quinazoline (1M1). Experimental structure, not a prediction.
What the evidence adds up to
In a randomised controlled trial of 151 patients with intermittent claudication, endovascular revascularisation produced faster initial improvement than supervised hospital-based exercise, but this advantage disappeared by six months. At six and twelve months, functional capacity and quality-of-life scores increased equally in both groups, and no significant difference in clinical success — defined as improvement by at least one Rutherford category — was found at either time point (adjusted odds ratio at six months 0.9, 99% CI 0.3 to 2.3; at twelve months 1.1, 99% CI 0.5 to 2.8). Fewer revascularised patients had ipsilateral symptoms at six months, but that difference was also gone by twelve months.
The majority of patients with intermittent claudication are managed conservatively, with smoking cessation and exercise therapy as first-line measures. A 1992 editorial noted that drug treatments for peripheral vascular disease are widely prescribed but that well-controlled trials are needed to establish whether any drug can improve functional capacity, slow atherosclerotic progression, or reduce cardiac and cerebrovascular events. No drug has been shown to achieve those goals in a definitive trial.
Intermittent claudication is the first symptom of peripheral arterial disease in many patients and is associated with systemic endothelial dysfunction. In claudicants, endothelial dysfunction correlates negatively with plasma levels of high-sensitivity C-reactive protein, suggesting inflammation plays a role. Whether interventions that improve endothelial function will reduce cardiovascular risk in these patients remains unclear.
What is still missing is a drug or combination of drugs proven in adequately powered, placebo-controlled trials to improve walking distance or reduce cardiovascular events in intermittent claudication. The existing evidence does not support routine use of any pharmacological agent for this condition, and the long-term equivalence of revascularisation and exercise means that decisions about invasive treatment must be made on an individual basis, with attention to patient preference and the durability of benefit beyond one year.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Radiology · 2009 · 157 citations
Intermittent Claudication: Clinical Effectiveness of Endovascular Revascularization versus Supervised Hospital-based Exercise Training—Randomized Controlled Trial
AbstractPURPOSE: To compare clinical success, functional capacity, and quality of life during 12 months after revascularization or supervised exercise training in patients with intermittent claudication. MATERIALS AND METHODS: This study had institutional review board approval, and all patients gave written informed consent. Between September 2002 and September 2005, 151 consecutive patients who presented with symptoms of intermittent claudication were randomly assigned to undergo either endovascular revascularization (angioplasty-first approach) (n = 76) or hospital-based supervised exercise (n = 75). The outcome measures were clinical success, functional capacity, and quality of life after 6 and 12 months. Clinical success was defined as improvement in at least one category in the Rutherford scale above the pretreatment level. Significance of differences between the groups was assessed with the unpaired t test, chi(2) test, or Mann-Whitney U test. To adjust outcomes for imbalances of baseline values, multivariable regression analysis was performed. RESULTS: Immediately after the start of treatment, patients who underwent revascularization improved more than patients who performed exercise in terms of clinical success (adjusted odds ratio [OR], 39; 99% confidence interval [CI]: 11, 131; P < .001), but this advantage was lost after 6 (adjusted OR, 0.9; 99% CI: 0.3, 2.3; P = .70) and 12 (adjusted OR, 1.1; 99% CI: 0.5, 2.8; P = .73) months. After revascularization, fewer patients showed signs of ipsilateral symptoms at 6 months compared with patients in the exercise group (adjusted OR, 0.4; 99% CI: 0.2, 0.9; P < .001), but no significant differences were demonstrated at 12 months. After both treatments, functional capacity and quality of life scores increased after 6 and 12 months, but no significant differences between the groups were demonstrated. CONCLUSION: After 6 and 12 months, patients with intermittent claudication benefited equally from either endovascular revascularization or supervised exercise. Improvement was, however, more immediate after revascularization.
Medical treatment of peripheral vascular disease: good or bad?
AbstractThe majority of patients with intermittent claudication are treated conservatively; smoking must be stopped and exercise therapy commenced. There are various classes of drugs that are widely prescribed for the treatment of peripheral vascular disease. In this editorial the medical treatment of peripheral vascular disease is claimed to achieve at least one of three goals: (1) improvement of the functional capability; (2) inhibition of the progression of the atherosclerotic and anatomical lesions; (3) reduction of the cardiac and cerebrovascular morbidity and mortality. Guidelines are given for well controlled trials for newly developed drugs for the treatment of peripheral vascular disease in the future.
AbstractIntermittent claudication is a painful, debilitating condition that reduces mobility in those affected and has a detrimental effect on quality of life. It is often the first symptom of peripheral arterial disease. This article explains the aetiology of intermittent claudication, the associated risk factors, vascular assessment and the nursing care involved in conservative treatment.
European Heart Journal Supplements · 2002 · 5 citations · open access
Intermittent claudication and endothelial dysfunction
AbstractThe endothelium regulates homeostasis in healthy blood vessels. When affected by injurious stimuli it becomes dysfunctional, thus eliciting changes that predispose to atherosclerosis. Patients with intermittent claudication show a systemic endothelial dysfunction that may result from a variety of factors. In particular, inflammation could play a key role because, in claudicants, endothelial dysfunction negatively correlates with plasma levels of high-sensitivity C-reactive protein, an acute-phase reactant. Future studies will clarify whether interventions that improve endothelial function will improve t he clinical outcome of patients with peripheral arterial disease by reducing their cardiovascular risk.
Journal of Clinical Medicine · 2023 · 2 citations · open access
The Ability to Look Beyond: The Treatment of Peripheral Arterial Disease
AbstractThis paper offers a practical overview of the contemporary management of patients with peripheral arterial disease presenting intermittent claudication (IC), including clinical and instrumental diagnosis, risk factors modification, medical management, and evidence-based revascularization indications and techniques. Decision making represents a crucial element in the management of the patient with IC; for this, we think a review of this type could be very useful, especially for non-vascular specialists.
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.
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