DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cerebral infarction — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCerebral infarction maps to a 12-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 infarction 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
prostaglandin-endoperoxide synthase 2 (PTGS2) — PTGS2 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 saldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5F1A · 2.38 Å · ligand 2-HYDROXYBENZOIC ACID (SAL). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 case-control study in a Chinese population examined eight genetic variants in five candidate genes among 292 patients with cerebral infarction and 259 healthy controls. No statistically significant differences in genotype frequencies were found for any single variant. However, a gene-gene interaction between the SG13S114 variant of ALOX5AP and the A6986G variant of CYP3A5 was identified, with a cross-validation consistency of 10 and a sign test score of 9 (P=0.0107). This two-locus interaction predicted a significantly higher risk of cerebral infarction, with an odds ratio of 1.804 (95% confidence interval 1.180–2.759, P=0.006) after adjustment for age, hypertension, and diabetes mellitus.
A 2024 study using mouse models of middle cerebral artery occlusion (MCAO) identified 1,517 differentially expressed genes in brain tissue. Pyroptosis-related genes Aim2, Casp8, Gsdmd, Naip2, Naip5, Naip6, and Trem2 were upregulated in MCAO mice from dataset GSE137482. In a separate dataset (GSE93376), Casp8, Gsdmd, and Trem2 were confirmed as significantly upregulated. In MCAO mice, TNF-α and pyroptosis-related proteins Casp8, Gsdmd, and Trem2 were significantly upregulated. In BV2 microglial cells treated with oxygen-glucose deprivation (OGD), Trem2 expression increased. Downregulating Trem2 in OGD-treated BV2 cells further increased pyroptosis, leading the authors to conclude that Trem2 is a protective factor regulating pyroptosis in cerebral infarction.
A 2006 study examined cytoskeleton and apoptosis-related gene expression in autopsy brain tissue from ten cerebral infarction patients. In the infarct core (area 0), no cell survival was observed, and all markers (MAP, GFAP, NF-200, bcl-2, factor VIII) were negative. In the peri-infarct area (area 1), MAP-2 and NF-200 immunoreactivity were dramatically downregulated. In more distant areas (areas 2 and 3), MAP-2 and NF-200 expression returned to normal levels. GFAP- and factor VIII-positive cells were absent from areas 0 and 1 but appeared in areas 2 and 3, with numbers strongly increased in the long phase of ischaemia. Bcl-2 immunoreactive cells were seen only in area 2.
What remains missing is any clinical trial testing a drug that targets these identified genes or pathways. The genetic association study is observational and has not been replicated in a larger or non-Chinese population. The mouse and autopsy studies describe molecular changes but do not test an intervention. No drug has been shown in these abstracts to reduce infarct size or improve functional outcome in patients. Funding for a prospective trial, a clear patient stratification strategy based on the ALOX5AP–CYP3A5 interaction, and a specific drug candidate are all 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.
Neuroreport · 2013 · 13 citations
Interaction between ALOX5AP and CYP3A5 gene variants significantly increases the risk for cerebral infarctions in Chinese
AbstractIn this study, we investigated associations between susceptibility genes and cerebral infarctions in a Chinese population, and whether gene-gene interactions increase the risk of cerebral infarctions. Overall, 292 patients with cerebral infarctions and 259 healthy control individuals were included. Eight variants in five candidate genes were examined for the risk of stroke, including the SG13S32 (rs9551963), SG13S42 (rs4769060), SG13S89 (rs4769874), and SG13S114 (rs10507391) variants of the 5-lipoxygenase activating protein (ALOX5AP) gene, the G860A (rs751141) variant of the soluble epoxide hydrolase (EPHX2) gene, the A1075C (rs1057910) variant of the CYP2C9*2 gene, the C430T (rs1799853) variant of the CYP2C9*3 gene, and the A6986G (rs776746) variant of the CYP3A5 gene. Gene-gene interactions were explored using generalized multifactor dimensionality reduction methods. There were no statistically significant differences in the frequencies of the genotypes of the eight candidate genes. The generalized multifactor dimensionality reduction analysis showed a significant gene-gene interaction between SG13S114 and A6986G, with scores of 10 for cross-validation consistency and 9 for the sign test (P=0.0107). These gene-gene interactions predicted a significantly higher risk of cerebral infarction (adjusted for age, hypertension, and diabetes mellitus; odds ratio=1.80495%, confidence interval: 1.180-2.759, P=0.006). A two-loci gene interaction confers a significantly higher risk for cerebral infarction. The combinational analysis used in this study may be helpful in the elucidation of genetic risk factors for common and complex diseases.
Study on pyroptosis-related genes Casp8, Gsdmd and Trem2 in mice with cerebral infarction
AbstractObjective Cerebral infarction is the main cause of death in patients with cerebrovascular diseases. Our research aimed to screen and validate pyroptosis-related genes in cerebral infarction for the targeted therapy of cerebral infarction. Methods and results A total of 1,517 differentially expressed genes (DEGs) were obtained by DESeq2 software analysis. Gene set enrichment analysis results indicated that genes of middle cerebral artery occlusion (MCAO) mice aged 3 months and 18 months were enriched in pyroptosis, respectively. Differentially expressed pyroptosis-related genes (including Aim2, Casp8, Gsdmd, Naip2, Naip5, Naip6 and Trem2) were obtained through intersection of DEGs and genes from pyroptosis Gene Ontology Term (GO:0070269), and they were up-regulated in the brain tissues of MCAO mice in GSE137482 . In addition, Casp8, Gsdmd, and Trem2 were verified to be significantly up-regulated in MCAO mice in GSE93376 . The evaluation of neurologic function and triphenyltetrazolium chloride staining showed that the MCAO mouse models were successfully constructed. Meanwhile, the expressions of TNF- α , pyroptosis-related proteins, Casp8, Gsdmd and Trem2 in MCAO mice were significantly up-regulated. We selected Trem2 for subsequent functional analysis. OGD treatment of BV2 cell in vitro significantly upregulated the expressions of Trem2. Subsequent downregulation of Trem2 expression in OGD-BV2 cells further increased the level of pyroptosis. Therefore, Trem2 is a protective factor regulating pyroptosis, thus influencing the progression of cerebral infarction. Conclusions Casp8, Gsdmd and Trem2 can regulate pyroptosis, thus affecting cerebral infarction.
Expression of cytoskeleton and apoptosis related genes after cerebral infarction
AbstractOBJECTIVE: The aim of the study was to investigate the expression and regulation of cytoskeleton and apoptosis related genes in several brain areas after cerebral infarction. METHODS: Tissues were collected from ten autopsy brains from cerebral infarction patients. Using immunohistochemistry, several cytoskeleton and apoptosis related genes were examined in these tissues. The genes included microtubule-associated protein (MAP), glial fibrillary acidic protein (GFAP), neurofilament protein (NF-200), apoptosis gene bc1-2 and factor VIII related antigen (F-VIII). Based on morphological changes in the damaged areas after infarction, the focus and the surrounding areas of injured brain were divided into four areas. RESULTS: In area 0, there was almost no cell survival after infraction, and all markers mentioned above were negative in this area. In addition, both MAP-2 and NF200 like immunoreactivities were dramatically down-regulated in area 1. However, in area 2 and area 3, MAP-2 and NF-200 expressed at normal level. GFAP- and F-VIII immunoreactive cells could hardly found in areas 0 and 1. In the short phase of ischemia, both GFAP and F-immmunoreactive cells could be seen in areas 2 and 3, and the number of GFAP and F (positive cells) was strongly increased in the long phase of ischemia. Bcl-2 immunoreactive cells were only seen in area 2. CONCLUSION: Cerebral infarction causes cell death and physipathological changes of cytoskeleton and apoptosis related genes.
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.
