DeCure for Preterm premature rupture of the membranes
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for preterm premature rupture of the membranes — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePreterm premature rupture of the membranes maps to a 6-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 preterm premature rupture of the membranes 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
calcium voltage-gated channel subunit alpha1 D (CACNA1D) — CACNA1D 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 clrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7UHG · 3.0 Å · ligand CHOLESTEROL (CLR). Experimental structure, not a prediction.
What the evidence adds up to
In a case-control study restricted to African American women, carriers of the rarer allele of the TNFα gene promoter polymorphism at position -308 were not significantly more common among all women who delivered preterm (24/55, 44%) than among term controls (33/110, 30%; P = 0.08, odds ratio 1.81). However, among the subgroup of women who delivered preterm specifically after preterm premature rupture of membranes (PPROM), carriers of the rarer allele were significantly more common (15/26, 58%) than controls (P = 0.008, odds ratio 3.18). The authors hypothesised that host hyperresponsiveness of the TNFα gene to genital tract infection may promote PPROM and subsequent preterm delivery.
PPROM occurs in about 3% of all pregnancies and accounts for one third of preterm births. A proteomic study of fetal membranes compared four groups of five cases each (discovery) and 30 cases each (validation): spontaneous preterm labour (sPTL), PPROM, full-term birth, and full-term premature rupture of membranes. Among 2,800 proteins identified, 62 showed statistical differences between preterm and full-term groups. Differentially expressed proteins included those involved in inflammation (HPGD), T cell activation (PTPRC), macrophage activation (CAPG, CD14, CD163), cell adhesion (ICAM, ITGAM), proteolysis (CTSG, ELANE, MMP9), antioxidant activity (MPO), extracellular matrix proteins (APMAP, COL4A1, LAMA2, LMNB1, LMNB2, FBLN2, CSRP1), and metabolism (PKM, ADPGK, ACOX1, ACSL3, ATP6AP1, CYBB). The authors concluded that inflammation is a major event and that proteolysis may play an important role in fetal membrane rupture.
A bacterial species implicated in PPROM and other obstetric complications, Sneathia amnii strain Sn35, was shown to adhere to, invade, and damage or kill various host cell lines in vitro. A putative virulence determinant was identified and a fragment expressed for antiserum production, but the antiserum was unable to prevent the cytopathogenic effects. Multiple review articles from 1993, 2005, and 2011 note that the management of PPROM remains controversial, that expectant management with antibiotics and steroids is increasingly advocated, and that the roles of tocolytic agents and strategies for membrane repair or prevention have not been definitively determined. The physiologic mechanisms leading to membrane rupture have not been fully elucidated.
What is still missing: large prospective genetic studies that stratify by PPROM subtype, validated biomarkers to identify women at risk, adequately powered randomised trials comparing management strategies, and any intervention that can prevent or repair membrane rupture in humans.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Obstetrics and Gynecology · 1999 · 207 citations · open access
Association of polymorphism within the promoter of the tumor necrosis factor α gene with increased risk of preterm premature rupture of the fetal membranes
AbstractOBJECTIVE: The rarer allele of a polymorphism within the promoter region at position -308 of the gene for tumor necrosis factor alpha is associated with increased gene transcription. In this study we tested the hypothesis that this rarer allele is associated with spontaneous preterm birth. STUDY DESIGN: We conducted a case-control study of women admitted to our labor and delivery unit. To assess data from a single racial group with a high incidence of preterm birth we restricted our analysis to African American women, who contributed 73.6% of the samples collected during the study period. Case patients (n = 55) were defined as women who were delivered before 37 weeks' gestation after idiopathic preterm labor or preterm premature rupture of membranes. Control subjects (n = 110) included women who were delivered after 37 weeks' gestation and had no history of preterm delivery. We also performed subgroup analyses of women with idiopathic preterm labor and delivery (n = 29) and women who were delivered preterm after preterm premature rupture of the fetal membranes (n = 26). RESULTS: Although carriers (homozygotes plus heterozygotes) of the rarer allele of the polymorphism at position -308 in the gene for tumor necrosis factor alpha were not significantly more common among women who were delivered preterm (n = 24/55, 44%) than among control subjects (n = 33/110, 30%, P =.08, odds ratio 1.81, 95% confidence interval 0.92-3.54), carriers of the rarer allele were more common among women who were delivered preterm after preterm premature rupture of membranes (n = 15/26, 58%) than among control subjects (P =.008, odds ratio 3.18, 95% confidence interval 1.33-7.83). CONCLUSIONS: Our results demonstrate an association between allelic variants of the polymorphism at position -308 in the gene for tumor necrosis factor alpha and preterm birth after preterm premature rupture of the fetal membranes. We hypothesize that host susceptibility to environmental factors, such as hyperresponsiveness of the gene for tumor necrosis factor alpha to genital tract infection, may promote preterm premature rupture of the fetal membranes and subsequent preterm delivery.
American Journal of Perinatology · 2005 · 45 citations
Preterm Premature Rupture of Membranes: Perspectives Surrounding Controversies in Management
AbstractPreterm premature rupture of the membranes (PPROM) occurs in approximately 3% of all pregnancies, and accounts for one third of all preterm births. Despite its prevalence, optimal management of PPROM remains largely undefined and lacks conformity. In this article, we review the pathophysiology of PPROM, and summarize the available literature describing various management strategies in an effort to define current controversies in the management of PPROM.
Frontiers in Physiology · 2020 · 33 citations · open access
Proteomic Study of Fetal Membrane: Inflammation-Triggered Proteolysis of Extracellular Matrix May Present a Pathogenic Pathway for Spontaneous Preterm Birth
AbstractINTRODUCTION: Spontaneous preterm birth (sPTB), which predominantly presents as spontaneous preterm labor (sPTL) or prelabor premature rupture of membranes (PPROM), is a syndrome that accounts for 5-10% of live births annually. The long-term morbidity in surviving preterm infants is significantly higher than that in full-term neonates. The causes of sPTB are complex and not fully understood. Human placenta, the maternal and fetal interface, is an environmental core of fetal intrauterine life, mediates fetal oxygen exchange, nutrient uptake, and waste elimination and functions as an immune-defense organ. In this study, the molecular signature of preterm birth placenta was assessed and compared to full-term placenta by proteomic profiling. MATERIALS AND METHODS: Four groups of fetal membranes (the amniochorionic membranes), with five cases in each group in the discovery study and 30 cases in each group for validation, were included: groups A: sPTL; B: PPROM; C: full-term birth (FTB); and D: full-term premature rupture of membrane (PROM). Fetal membranes were dissected and used for proteome quantification study. Maxquant and Perseus were used for protein quantitation and statistical analysis. Both fetal membranes and placental villi samples were used to validate proteomic discovery. RESULTS: Proteomics analysis of fetal membranes identified 2,800 proteins across four groups. Sixty-two proteins show statistical differences between the preterm and full-term groups. Among these differentially expressed proteins are (1) proteins involved in inflammation (HPGD), T cell activation (PTPRC), macrophage activation (CAPG, CD14, and CD163), (2) cell adhesion (ICAM and ITGAM), (3) proteolysis (CTSG, ELANE, and MMP9), (4) antioxidant (MPO), (5) extracellular matrix (ECM) proteins (APMAP, COL4A1, LAMA2, LMNB1, LMNB2, FBLN2, and CSRP1) and (6) metabolism of glycolysis (PKM and ADPGK), fatty acid synthesis (ACOX1 and ACSL3), and energy biosynthesis (ATP6AP1 and CYBB). CONCLUSION: Our molecular signature study of preterm fetal membranes revealed inflammation as a major event, which is inconsistent with previous findings. Proteolysis may play an important role in fetal membrane rupture. Extracellular matrix s have been altered in preterm fetal membranes due to proteolysis. Metabolism was also altered in preterm fetal membranes. The molecular changes in the fetal membranes provided a significant molecular signature for PPROM in preterm syndrome.
AbstractAlthough the etiology of preterm premature rupture of membranes (PPROM) is probably multifactorial, recent literature has indicated that infectious processes may play an important role. The management of PPROM is still controversial, requiring individualization of care for each patient. Expectant management is increasingly advocated. The role of adjuvant therapies using antibiotics, steroids, and tocolytic agents remains to be definitively determined. The following review article addresses recent literature involving the PPROM patient.
Considerations in Membrane Resealing After Preterm PROM
AbstractCurrent management of preterm premature rupture of the membranes centers around the expectant management with antibiotics and steroid therapy. Membrane rupture seems to be the result of a mechanical event. Studying the physical properties of the membranes may help to gain understanding of the nature and causes of membrane rupture. This article reviews membrane mechanics, advances in membrane healing, and strategies in the prevention of membrane rupture. The physiologic mechanisms that lead to membrane rupture have not yet been fully elucidated. Models that test the biomechanics of the membranes should be used to develop strategies for repair or prevention.
The Characterization of a Putative Virulence Factor Expressed By Sneathia amnii
AbstractPreterm birth, defined at birth before 37 weeks gestation, affects millions of newborns worldwide every year. Preterm birth is a leading cause of infant morbidity and mortality. One major cause of preterm birth is preterm premature rupture of membranes (PPROM), which can be triggered by bacterial infection and inflammation. A bacterial species that has been implicated in preterm birth and other obstetric complications is Sneathia amnii. The goals of this study were to observe cytopathogenic effects caused by S. amnii strain Sn35 and identify putative virulence factors causing those effects. Sn35 was able to adhere to, invade, and damage/kill various host cell lines. We characterized these virulence attributes. A putative virulence determinant was identified, and a fragment of the protein was expressed for polyclonal antiserum production. Antiserum was used to characterize the expression and subcellular localization of the protein in Sn35. However, antiserum was unable to prevent cytopathogenic effects.
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.
