DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for severe pre-eclampsia — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSevere pre-eclampsia maps to a 13-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 severe pre-eclampsia 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
adrenoceptor beta 3 (ADRB3) — ADRB3 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 aledrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9IJE · 2.34 Å · ligand L-EPINEPHRINE (ALE). Experimental structure, not a prediction.
What the evidence adds up to
A 2017 Cochrane review of six randomised trials (748 women) compared early planned delivery (interventionist care) with delayed delivery (expectant care) for severe pre-eclampsia between 24 and 34 weeks’ gestation. No maternal deaths occurred in the two trials that reported them (320 women). The evidence was too weak to determine whether interventionist care reduced eclampsia (risk ratio 0.98, 95% CI 0.06 to 15.58; two studies, 359 women) or pulmonary oedema (risk ratio 0.45, 95% CI 0.07 to 3.00; two studies, 415 women). There was no clear difference in HELLP syndrome (risk ratio 1.09, 95% CI 0.62 to 1.91; two studies, 359 women; low-quality evidence). No study reported stroke. Caesarean section rates were similar (average risk ratio 1.01, 95% CI 0.91 to 1.12; six studies, 745 women).
For the baby, perinatal deaths were not clearly different (risk ratio 1.11, 95% CI 0.62 to 1.99; three studies, 343 women; low-quality evidence). Babies in the interventionist group had more intraventricular haemorrhage (risk ratio 1.94, 95% CI 1.15 to 3.29; two studies, 537 women; moderate-quality evidence), more respiratory distress from hyaline membrane disease (risk ratio 2.30, 95% CI 1.39 to 3.81; two studies, 133 women), required more ventilation (risk ratio 1.50, 95% CI 1.11 to 2.02; two studies, 300 women), and were born about ten days earlier (mean difference −9.91 days, 95% CI −16.37 to −3.45; four studies, 425 women). They were less likely to be small-for-gestational age (risk ratio 0.38, 95% CI 0.24 to 0.61; three studies, 400 women). The review authors concluded that an expectant approach may reduce neonatal morbidity, but that the evidence came from only six trials and further large, high-quality studies are needed.
Two small gene-expression studies identified molecular changes in pre-eclamptic placentas. A 2007 microarray study of two pre-eclamptic patients with intrauterine growth restriction versus three healthy controls found nine angiogenesis-related genes downregulated (ECGF1, JAG1, Palladin, COL18A1, TNFSF12, VEGF, ANPEP, PDGFRA, SERPIN12) and four upregulated (EPAS1, FLT1, SIGLE10, ANG4). Real-time RT-PCR confirmed the changes for JAG1, COL18A1 and FLT1. A 2022 study of 60 pre-eclampsia patients and 60 healthy pregnancies reported that EID1 mRNA was decreased in pre-eclamptic placental tissue, especially in early-onset cases, and that lower EID1 was associated with more severe clinical presentation and a higher rate of fetal growth restriction. In cultured HTR-8/SVneo trophoblast cells, forced expression of EID1 increased proliferation, migration and invasion, while silencing it had the opposite effect; Akt/β-catenin signalling was activated with EID1 overexpression and deactivated after silencing.
What is still missing: the Cochrane review highlights the need for larger, higher-quality trials to confirm whether expectant management is safe for the mother. The gene-expression studies are too small (two patients versus three controls; 60 versus 60) to support any therapeutic target, and neither tested a drug. No randomised trial of a pharmacological intervention for severe pre-eclampsia is reported in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cochrane Database of Systematic Reviews · 2013 · 134 citations · open access
Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks' gestation
AbstractBACKGROUND: Severe pre-eclampsia can cause significant mortality and morbidity for both mother and child, particularly when it occurs remote from term, between 24 and 34 weeks' gestation. The only known cure for this disease is delivery. Some obstetricians advocate early delivery to ensure that the development of serious maternal complications, such as eclampsia (fits) and kidney failure are prevented. Others prefer a more expectant approach, delaying delivery in an attempt to reduce the mortality and morbidity for the child that is associated with being born too early. OBJECTIVES: To evaluate the comparative benefits and risks of a policy of early delivery by induction of labour or by caesarean section, after sufficient time has elapsed to administer corticosteroids, and allow them to take effect; with a policy of delaying delivery (expectant care) for women with severe pre-eclampsia between 24 and 34 weeks' gestation. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) on 27 November 2017, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing the two intervention strategies for women with early onset, severe pre-eclampsia. Trials reported in an abstract were eligible for inclusion, as were cluster-trial designs. We excluded quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. We assessed the quality of the evidence for specified outcomes using the GRADE approach. MAIN RESULTS: We included six trials, with a total of 748 women in this review. All trials included women in whom there was no overriding indication for immediate delivery in the fetal or maternal interest. Half of the trials were at low risk of bias for methods of randomisation and allocation concealment; and four trials were at low risk for selective reporting. For most other domains, risk of bias was unclear. There were insufficient data for reliable conclusions about the comparative effects on most outcomes for the mother. Two studies reported on maternal deaths; neither study reported any deaths (two studies; 320 women; low-quality evidence). It was uncertain whether interventionist care reduced eclampsia (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.06 to 15.58; two studies; 359 women) or pulmonary oedema (RR 0.45, 95% CI 0.07 to 3.00; two studies; 415 women), because the quality of the evidence for these outcomes was very low. Evidence from two studies suggested little or no clear difference between the interventionist and expectant care groups for HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome (RR 1.09, 95% CI 0.62 to 1.91; two studies; 359 women; low-quality evidence). No study reported on stroke. With the addition of data from two studies for this update, there was now evidence to suggest that interventionist care probably made little or no difference to the incidence of caesarean section (average RR 1.01, 95% CI 0.91 to 1.12; six studies; 745 women; Heterogeneity: Tau² = 0.01; I² = 63%).For the baby, there was insufficient evidence to draw reliable conclusions about the effects on perinatal deaths (RR 1.11, 95% CI 0.62 to 1.99; three studies; 343 women; low-quality evidence). Babies whose mothers had been allocated to the interventionist group had more intraventricular haemorrhage (RR 1.94, 95% CI 1.15 to 3.29; two studies; 537 women; moderate-quality evidence), more respiratory distress caused by hyaline membrane disease (RR 2.30, 95% CI 1.39 to 3.81; two studies; 133 women), required more ventilation (RR 1.50, 95% CI 1.11 to 2.02; two studies; 300 women), and were more likely to have a lower gestation at birth (mean difference (MD) -9.91 days, 95% CI -16.37 to -3.45 days; four studies; 425 women; Heterogeneity: Tau² = 31.74; I² = 76%). However, babies whose mothers had been allocated to the interventionist group were no more likely to be admitted to neonatal intensive care (average RR 1.19, 95% CI 0.89 to 1.60; three studies; 400 infants; Heterogeneity: Tau² = 0.05; I² = 84%). Babies born to mothers in the interventionist groups were more likely to have a longer stay in the neonatal intensive care unit (MD 7.38 days, 95% CI -0.45 to 15.20 days; three studies; 400 women; Heterogeneity: Tau² = 40.93, I² = 85%) and were less likely to be small-for-gestational age (RR 0.38, 95% CI 0.24 to 0.61; three studies; 400 women). There were no clear differences between the two strategies for any other outcomes. AUTHORS' CONCLUSIONS: This review suggested that an expectant approach to the management of women with severe early onset pre-eclampsia may be associated with decreased morbidity for the baby. However, this evidence was based on data from only six trials. Further large, high-quality trials are needed to confirm or refute these findings, and establish if this approach is safe for the mother.
Altered expression of angiogenesis-related placental genes in pre-eclampsia associated with intrauterine growth restriction
AbstractAIM: The normal endovascular invasion of trophoblast cells and spiral artery remodeling are impaired in pre-eclampsia. Neither the circulating factor secreted by the placenta nor the cause of the widespread endothelial dysfunction in pre-eclampsia has yet been identified. In an attempt to identify novel factors, we performed a gene expression profiling study of placental tissue from women with and without pre-eclampsia. MATERIAL AND METHODS: The study group comprised two pre-eclamptic patients with intrauterine growth restriction while the control group comprised three healthy women with uncomplicated pregnancies. Gene expression was studied using Affymetrix Human Genome U133 Plus 2 micro arrays. We focused on genes associated with angiogenesis. Some of the micro array analysis results were verified using real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Gene expression profiling revealed that the expression level of nine genes--ECGF1, JAG1, Palladin, COL18A1, TNFSF12, VEGF, ANPEP, PDGFRA and SERPIN12 - was downregulated whereas the level of four genes--EPAS1, FLT1, SIGLE10 and ANG4--was upregulated in the study group compared with the control group. The real-time RT-PCR results from JAG1, COL18A1 and FLT1 genes were in accordance with the gene expression results. CONCLUSION: Our results show new targets for research to understand the mechanisms leading to pre-eclampsia.
Preeclampsia and future cardiovascular risk: A point of view from the clearance of plasma vasoactive amines
AbstractOBJECTIVE: To summarize the reported evidence on the relationship between vasoactive amines and preeclampsia. METHODS: A literature search was conducted in MEDLINE/PubMed and EMBASE. RESULTS: The summarized results are as follows: (1) Menstruation can effectively eliminate vasoactive amines norepinephrine, serotonin and histamine. (2) Pregnancy increases norepinephrine production due to fetal brain development and decreases vasoactive-amine elimination due to amenorrhea. (3) Preeclampsia is associated with a low renal and/or sweating capacity, or in rare cases, with increased norepinephrine production due to maternal pheochromocytoma and fetal neuroblastoma. CONCLUSION: Preeclampsia is mainly due to decreased excretion of norepinephrine and other vasoactive amines.
Folia Histochemica et Cytobiologica · 2022 · 5 citations · open access
EID1 plays a protective role in early-onset pre-eclampsia via promoting proliferation and invasion in trophoblast cells
AbstractINTRODUCTION: Pre-eclampsia is a pregnancy-specific syndrome, which is partly due to abnormal proliferation and invasion of trophoblast cells. EP300 interacting inhibitor of differentiation 1 (EID1) participates in cell proliferation and invasion. This study aims to investigate the roles of EID1 in trophoblast cells and pre-eclampsia. MATERIAL AND METHODS: The expression of EID1 in placental tissues from 60 women with pre-eclampsia and 60 health pregnancies was detected by real-time PCR and immunohistochemical staining. EID1 was overexpressed or silenced by transfection of plasmid or siRNA in HTR-8/SVneo trophoblast cells, and then cell proliferation, cell cycle transition, migration, and invasion were determined by CCK-8 assay, flow cytometry, immunofluorescent staining, immunoblotting, and transwell assays. In addition, the activity of Akt/b-catenin signaling was measured by immunofluorescent staining and Western blot. RESULTS: EID1 mRNA level was decreased in placental tissues of pre-eclampsia patients, especially early-onset pre-eclampsia, accompanied by more severe clinical manifestation and a higher rate of fetal growth restriction (FGR). Gain- and loss-of-function experiments demonstrated that EID1 promoted proliferation and cell cycle transition, migration, and invasion in HTR-8/SVneo cells and its knockdown played opposite roles, suggesting that EID1 may be required for normal gestation. Akt/b-catenin signaling was activated after EID1 forced expression and deactivated after its silencing. CONCLUSIONS: EID1 promoted proliferation and invasion of cultured trophoblast cells with possible involvement of Akt/b-catenin signaling. These findings may provide novel insights for the diagnosis and treatment of early-onset pre-eclampsia in a clinic.
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.
