DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for cerebral atherosclerosis — 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 moduleCerebral atherosclerosis 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 cerebral atherosclerosis 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
protein tyrosine phosphatase receptor type D (PTPRD) — PTPRD 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 flcdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2YD6 · 1.35 Å · ligand CITRATE ANION (FLC). Experimental structure, not a prediction.
What the evidence adds up to
A 2018 prospective cohort study of 1,367 consecutive patients who underwent coronary artery bypass grafting (CABG) between 2004 and 2007 used preoperative magnetic resonance angiography to classify patients by the location of cerebral atherosclerosis, defined as steno-occlusion of 50% or more. Over a median follow-up of 9.2 years, 20.3% of patients had intracranial cerebral atherosclerosis (ICAS) only, 19.7% had extracranial cerebral atherosclerosis (ECAS) only, and 25.4% had both. Having ICAS only (hazard ratio 5.07; 95% CI 1.37–18.75; p = 0.015) and having both ICAS and ECAS (hazard ratio 8.43; 95% CI 2.48–28.61; p = 0.001) independently predicted stroke within 14 days of surgery, whereas ECAS only did not (hazard ratio 1.71; 95% CI 0.35–8.50; p = 0.509). For long-term mortality, ICAS only was not independently associated (hazard ratio 1.22; 95% CI 0.90–1.65; p = 0.207), but ECAS only (hazard ratio 1.42; 95% CI 1.05–1.90; p = 0.021) and combined ICAS and ECAS (hazard ratio 1.58; 95% CI 1.20–2.07; p = 0.001) were.
A 2025 review describes cerebral atherosclerosis as a progressive pathological process causing stenosis of medium and large calibre cerebral arteries. It states that cerebral atherosclerosis underlies a large number of stroke cases, predominantly the atherothrombotic subtype, determines the risk of recurrent ischaemic events, and negatively impacts patient mortality. The review also says cerebral atherosclerosis significantly increases the risk of chronic cerebrovascular disease, attributing this to increased vascular wall stiffness, reduced vascular reactivity, impaired autoregulation, and high risk of microembolization. It lists causes and mechanisms as multifactorial, including metabolic disorders, endothelial dysfunction, neuroinflammation, oxidative stress, and cellular apoptosis.
A 1961 presidential address to the Chicago Neurological Society noted that large numbers of persons are affected by cerebral atherosclerosis, that it frequently causes crippling disability or sudden death, and that therapeutic weapons being used for the condition still needed proper assessment. The address stated that early concepts of cerebrovascular disease were relatively simple, with a segment of brain alleged to suffer sudden loss of function because of occlusion or rupture of its nutrient vessel, and that it had become apparent that many anatomical and physiological factors affect the clinical manifestations, including collateral blood supply and stenosis.
No drug treatment is mentioned in any of these abstracts. What is still missing is any randomised controlled trial testing a pharmacological intervention for cerebral atherosclerosis itself, as opposed to observational studies of prognosis or reviews of pathophysiology. Also missing is a trial design that stratifies patients by the location of their atherosclerosis (intracranial versus extracranial), given the 2018 data suggesting these have different prognostic implications. Funding for such a trial, and a clear patient stratification strategy, remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cerebrovascular Diseases · 2018 · 7 citations
The Impact of Cerebral Atherosclerosis According to Location on Prognosis after Coronary Artery Bypass Grafting
AbstractBACKGROUND: In the previous prospective observational study, we found that cerebral atherosclerosis is an independent predictor of acute stroke after coronary artery bypass grafting (CABG). However, it is unknown whether intracranial cerebral atherosclerosis (ICAS) is important as much as extracranial cerebral atherosclerosis (ECAS) in estimating the risk of post-CABG adverse events. Extending the previous study, we aimed to investigate the immediate and long-term prognostic value of the location of cerebral atherosclerosis in CABG patients. METHODS: This follow-up study of previously reported prospective cohort included 1,367 consecutive patients who received CABG between 2004 and 2007. All patients underwent preoperative magnetic resonance angiography (MRA) to assess intracranial and ECAS, both defined by significant steno-occlusion (≥50%). Participants were classified into 4 groups according to the location of cerebral atherosclerosis: no cerebral atherosclerosis, ECAS only, ICAS only, and ECAS + ICAS. Post-CABG stroke within 14 days (immediate outcome) and mortality (long-term outcome) following CABG were compared between the groups. Survival data for all participants through June 2016 were obtained from the Korean National Registry of Vital Statistics. The Cox proportional hazards model was used to estimate the hazard ratio (HR) of post-CABG stroke and mortality; patients lacking cerebral atherosclerosis were defined as the reference group. RESULTS: The median follow-up duration after CABG was 9.2 years (interquartile range 8.4-10.2 years). Of the participants, 278 (20.3%) patients had ICAS only, while 269 (19.7%) and 347 (25.4%) showed ECAS only and ECAS + ICAS, respectively, in their preoperative MRA. Having ICAS only (HR 5.07; 95% CI 1.37-18.75; p = 0.015) and having ECAS + ICAS (HR 8.43; 95% CI, 2.48-28.61; p = 0.001) independently predicted the immediate stroke, whereas being with ECAS only did not (HR 1.71; 95% CI 0.35-8.50; p = 0.509). Conversely, ICAS-only status was not independently associated with long-term mortality (HR 1.22; 95% CI 0.90-1.65; p = 0.207), whereas ECAS-only status (HR 1.42; 95% CI 1.05-1.90; p = 0.021) and ECAS + ICAS status (HR 1.58; 95% CI 1.20-2.07; p = 0.001) showed independent associations. CONCLUSIONS: Over 10 years of follow-up, cerebral atherosclerosis significantly associated with the development of adverse outcomes after CABG. The prognostic value of ICAS might be different from that of ECAS; immediate post-CABG stroke was more closely associated with ICAS, whereas there was a closer association between long-term post-CABG mortality and ECAS.
Effective Pharmacotherapy · 2025 · 0 citations · open access
Role of Cerebral Atherosclerosis in the Development of Acute and Chronic Cerebrovascular Disease
AbstractCerebral atherosclerosis (CA) is a progressive pathological process that causes stenosis of the cerebral vessels, mainly medium and large caliber arteries. CA underlies a large number of stroke cases, predominantly of the atherothrombotic subtype, determines the risk of recurrent ischemic events, and also negatively impacts patient mortality. Furthermore, СА significantly increases the risk of chronic cerebrovascular disease. This is largely due to increased vascular wall stiffness, reduced vascular reactivity, impaired autoregulation, and high risk of microembolization. The causes and mechanisms of CA are multifactorial and include metabolic disorders, endothelial dysfunction, neuroinflammation, oxidative stress, cellular apoptosis, and many other. This review is dedicated to the role of CA in the development of both acute and chronic cerebrovascular pathology.
Abstract<h3>Presidential Address: Some Reflections on the Clinical Aspects of Cerebral Atherosclerosis.</h3> DR. MEYER BROWN. Cerebral atherosclerosis is a very important subject because large numbers of persons are affected with this condition, because it frequently causes crippling disability or sudden death, because it requires the cooperative efforts of neurologist, internist, pathologist, biochemist, and more recently neurosurgeon, because therapeutic weapons that are being used for this condition still need proper assessment, and finally because we are woefully ignorant as to the precise pathophysiologic process which is taking place in each patient with this condition. Early concepts of cerebrovascular disease were relatively simple. A segment of the brain was alleged to suffer a sudden loss of function because of occlusion or rupture of its nutrient vessel. It soon became apparent that many anatomical and physiological factors affect the clinical manifestations of cerebral atherosclerosis. These include such intracranial factors as collateral blood supply, stenosis
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.
