DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital factor XII deficiency — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital factor XII deficiency maps to a 2-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 congenital factor xii deficiency 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
coagulation factor XII (F12) — F12 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6X0T · 1.388 Å · ligand (2S)-1-(N,3-dicyclohexyl-D-alanyl)-4-[(4R,5S)-4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-yl]-N-[(thiophen-2-yl)methyl]piperazine-2-carboxamide (UJ7). Experimental structure, not a prediction.
What the evidence adds up to
A 2007 systematic review and meta-analysis of 14 studies found that factor XII deficiency is significantly associated with recurrent miscarriage. Among 1,096 women across five studies, the odds ratio was 18.11 (95% CI 5.52–59.39), with minimal heterogeneity. The same review found no significant association for factor XII C46T polymorphism (OR 1.07, 95% CI 0.52–2.22), plasminogen activator inhibitor-1 4G/5G polymorphism (OR 1.65, 95% CI 0.92–2.95), or factor XIII Val34Leu and Tyr204Phe polymorphisms. The authors noted that only a small minority of studies ascertained miscarriage according to specific criteria, and none provided equal examination for confounders in cases and controls.
A 2008 genetic study of 29 patients with congenital factor XII deficiency from nine families reported that 11 patients had factor XII activity and antigen at or below 1% and traces of antigen, consistent with homozygote phenotype. Seven patients were true homozygotes for the -8G>C promoter mutation. The remaining patients with a homozygote-like phenotype were compound heterozygotes for two distinct mutations, including three new mutations: Q501STOP in exon 13, P547L in exon 14, and -13C>T in the promoter. All compound heterozygotes showed very low factor XII activity and antigen, similar to homozygotes. The -8G>C mutation was widely diffused in this group from a limited geographical area, suggesting a founder effect. The new mutations were not present in 98 normal persons of the same geographical background.
A 1983 case report describes the first reported case of factor XI deficiency in a child from India who underwent pulmonary valvulotomy. The child received plasma infusion to sustain factor XI levels at about 40% of normal before and for 10 days after surgery, and did not experience excessive or delayed haemorrhage. A 2016 study of a family with congenital factor VII deficiency identified a homozygous mutation c.572-1G>A in the proband, with both parents being carriers, and performed prenatal diagnosis by amniocentesis.
What is still missing: no prospective trial has tested whether correcting factor XII deficiency reduces miscarriage rates in affected women. The meta-analysis relied on retrospective case-control studies with inconsistent miscarriage definitions and unadjusted confounders. No data exist on optimal factor XII replacement strategy, target levels, or duration of treatment during pregnancy. The genetic studies describe mutations but do not link specific genotypes to miscarriage risk or treatment response. No funding has been committed to a randomised trial of factor XII replacement in pregnant women with recurrent miscarriage and confirmed deficiency.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Obstetrics and Gynecology · 2007 · 68 citations
Fibrinolytic Defects and Recurrent Miscarriage
AbstractOBJECTIVE: To systematically review evidence of the association between fibrinolytic defects and recurrent miscarriage. DATA SOURCES: MEDLINE, EMBASE, and references of retrieved articles (last update September 2006) were used. METHODS OF STUDY SELECTION: Studies comparing the prevalence of fibrinolytic defects in patients with recurrent miscarriage and control women were reviewed. Of 111 potentially relevant studies, data from 14 were integrated with meta-analytic techniques and were presented as odds ratios (ORs). TABULATION, INTEGRATION, AND RESULTS: Plasminogen activator inhibitor-1 4G/5G polymorphism (OR 1.65, 95% confidence interval [CI] 0.92-2.95) and increased plasminogen activator inhibitor activity were not significantly associated with recurrent miscarriage, although the latter showed profound heterogeneity across studies. Although factor XII C46T polymorphism is not associated with recurrent miscarriage (OR 1.07, 95% CI 0.52-2.22), factor XII deficiency is significantly associated (five studies, 1,096 women; OR 18.11, 95% CI 5.52-59.39), with minimal heterogeneity across studies. Factor XIII Val34Leu and Tyr204Phe polymorphisms were not associated with recurrent miscarriage (OR 1.24, 95% CI 0.46-3.34 and OR 2.61, 95% CI 0.45-15.16, respectively). There were no eligible studies found for the rest of the factors searched (urokinase-type plasminogen activator, tissue-type plasminogen activator, kallicrein, a2-antiplasmin, a2-macroglobulin, thrombin-activated thrombolysis inhibitor, and factor XI). Only a small minority of studies ascertained miscarriage according to specific criteria, and none of the studies provided equal examination for confounders in cases and controls. CONCLUSION: Factor XII deficiency is associated with recurrent miscarriage. Data on the other factors either fail to show association or are quite limited.
Genetic study in patients with factor XII deficiency: a report of three new mutations exon 13 (Q501STOP), exon 14 (P547L) and –13C>T promoter region in three compound heterozygotes
AbstractA group of 29 patients with congenital factor XII (FXII) deficiency belonging to nine distinct families have been investigated. All were cases of true deficiency in the sense that there was no discrepancy between FXII activity and FXII antigen. From a clotting point of view, 11 patients appeared homozygous, as both FXII activity and antigen were very low (< or =1% and traces of antigen). In other words, they were cases with no cross-reactivity material. In the heterozygotes, FXII activity and antigen were about 50% of normal in all cases. The molecular studies revealed that seven patients were real homozygotes for the mutation -8G>C in the promoter region confirming the conclusions reported by coagulation tests. On the contrary, the remaining patients with a homozygote-like phenotype were instead found to be compound heterozygous for two distinct mutations. Three of these mutations were new mutations, namely the combination of -8G to C with 501Q to T (exon 13), 547P to L (exon 14) and -13C to T in the promoter, respectively. The remaining mutations seen were not new. It is interesting that all compound heterozygotes showed a clotting and immunological pattern similar to that shown by homozygotes, namely very low FXII activity and antigen. The new mutations were not present in the group of 98 normal persons of both sexes with the same geographical background. The wide diffusion of the -8G>C mutation in this group of patients coming from a limited geographical area suggests a founder effect. The significance and importance of genetic analysis in addition to clotting and immunological studies in FXII deficiency is emphasized.
The Thoracic and Cardiovascular Surgeon · 1983 · 3 citations
Pulmonary Valvulotomy in Factor XI Deficiency
AbstractThis is the first reported case in the English literature of Factor XI deficiency in a child from India. He underwent open-heart surgery and pulmonary valvulotomy without excessive or delayed hemorrhage using plasma infusion to sustain Factor XI levels at about 40% of normal before, and for 10 days after surgery. The management of this child is presented as an approach to patients with Factor XI deficiency who require major surgery.
[Mutation analysis and prenatal diagnosis for a family affected with congenital factor VII deficiency].
AbstractOBJECTIVE: To provide mutation analysis and prenatal diagnosis for a family affected with congenital factor VII(FVII) deficiency. METHODS: DNA was extracted from peripheral blood samples from the proband and his parents. All exons and flanking sequence of the FVII gene were amplified with PCR and subjected to direct sequencing. Prenatal diagnosis was performed by amniocentesis. RESULTS: A homozygous mutation (NM_000131.3) c.572-1G>A was identified in the proband. Both parents of the fetus were carriers of the mutation. CONCLUSION: A method for molecular diagnosis of congenital factor VII deficiency was established and successfully applied for an affected family.
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.
