DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital afibrinogenemia — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital afibrinogenemia maps to a 4-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 afibrinogenemia 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
fibrinogen alpha chain (FGA) — FGA 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 galdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3GHG · 2.9 Å · ligand beta-D-galactopyranose (GAL). Experimental structure, not a prediction.
What the evidence adds up to
Congenital afibrinogenemia is a rare autosomal recessive disorder defined by the complete absence of detectable fibrinogen. A 2003 study identified a compound heterozygote for two mutations in the FGB gene: an N-terminal nonsense mutation W47X and a missense mutation G444S. Coexpression experiments showed that fibrinogen molecules containing the mutant beta chain assembled inside the cell but were not secreted, confirming the pathogenic mechanism. The same study noted that the great majority of causative mutations are null mutations located in the FGA gene, though mutations in FGG and FGB have also been found.
The mainstay of treatment for acute bleeding or perioperative management is replacement with fibrinogen concentrate or fibrinogen-containing blood products. A 2020 case report described a 6-year-old girl who developed a severe allergic reaction to multiple fibrinogen-containing products and became refractory to treatment because of a presumed inhibitor to fibrinogen. A 2018 case report documented the first use of recombinant fibrinogen during a liver transplant in a patient with congenital afibrinogenemia, noting that historically fresh frozen plasma and cryoprecipitate had been used to manage coagulopathy during such procedures.
Haemorrhagic manifestations vary from minimal to catastrophic. A 2017 report listed fatal umbilical cord haemorrhage as a possible first manifestation, along with later bleeding from mucosal surfaces including epistaxis, menorrhagia, gastrointestinal bleeding, haemorrhage into muscles and joints, intracranial bleeding, spontaneous abortions, and spontaneous splenic rupture. Thrombotic manifestations can also occur, attributed to impaired thrombin inhibition. A 2016 case report noted that a little more than 250 cases had been published up to that point, and described a 3.5-year-old child hospitalised for haematemesis of medium abundance.
What is still missing is a systematic understanding of why some patients develop neutralising antibodies or anaphylaxis to replacement therapy, and whether any alternative treatment strategies exist for those who become refractory. No large-scale clinical trial data exist to guide the choice between plasma-derived and recombinant fibrinogen products, and the rarity of the disorder makes patient stratification by genotype or bleeding phenotype difficult to achieve without coordinated international registries.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 2003 · 40 citations · open access
Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion
AbstractCongenital afibrinogenemia is a rare autosomal recessive disorder characterized by complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease: a homozygous deletion of approximately 11 kb of the fibrinogen alpha-chain gene (FGA). Subsequent studies revealed that the great majority of afibrinogenemia mutations are localized in FGA, but mutations were also found in FGG and FGB. Apart from 3 missense mutations identified in the C-terminal portion of FGB, all fibrinogen gene mutations responsible for afibrinogenemia are null. In this study, a young boy with afibrinogenemia was found to be a compound heterozygote for 2 mutations in FGB: an N-terminal nonsense mutation W47X (exon 2) and a missense mutation (G444S, exon 8). Coexpression of the FGB G444S mutant cDNA in combination with wild-type FGA and FGG cDNAs demonstrated that fibrinogen molecules containing the mutant beta chain are able to assemble but are not secreted into the media, confirming the pathogenic nature of the identified mutation.
Asian Cardiovascular and Thoracic Annals · 2013 · 6 citations
Percutaneous coronary intervention in a case of afibrinogenemia
AbstractCongenital afibrinogenemia is a rare autosomic recessive blood disorder. A 30-year-old lady, known to have congenital afibrinogenemia, presented with acute anterior myocardial infarction. We managed her with dual antiplatelet therapy and atorvastatin, but her chest pain did not subside and she was transferred to the catheterization laboratory. A proximal left anterior descending artery occlusion was crossed with a floppy wire. Angioplasty was performed successfully with a bare metal stent, and her symptoms resolved completely.
Journal of Pediatric Hematology/Oncology · 2020 · 4 citations
Blood, Sweat, and Fears: A Novel Mutation Associated With Anaphylaxis and Nonresponse in a Patient With Afibrinogenemia
AbstractCongenital afibrinogenemia is a rare disorder characterized by a lack of detectable fibrinogen. The mainstay of treatment for acute bleeding episodes or perioperative management is replacement with fibrinogen concentrate or fibrinogen-containing blood products. The development of neutralizing antibodies and severe allergic reactions to fibrinogen replacement is rarely reported in afibrinogenemia patients. Here the treatment regimen is described for a 6-year-old girl with a severe allergic reaction to multiple fibrinogen-containing products who became refractory to treatment because of a presumed inhibitor to fibrinogen.
Experimental and Clinical Transplantation · 2018 · 3 citations
Administering RiaSTAP for Congenital Afibrinogenemia During Liver Transplant
AbstractLiver transplant has occasionally been performed in the presence of congenital afibrinogenemia and has been rarely used to treat it. Historically, to safely manage coagulopathy during transplant, these patients have been administered a combination of fresh frozen plasma and cryoprecipitate. In this case report, we discuss the first reported use of recombinant fibrinogen to treat such a patient and the decision-making process considered to balance the thrombotic and hemorrhagic risks.
Clinical Medical Reviews and Case Reports · 2017 · 2 citations · open access
Management of Congenital Afibrinogenemia: Report of Two Cases
AbstractCongenital afibrinogenemia is a rare bleeding disorder. Hemorrhagic manifestations vary from minimal to catastrophic bleed. It may include fatal umbilical cord hemorrhage as the first disease manifestation. In later life, the disorder may be associated with bleeding from mucosal surfaces including epistaxis, menorrhagia, gastrointestinal bleeding, hemorrhage into muscles and joints and intracranial bleeding, spontaneous abortions, and/or spontaneous splenic rupture. Thrombotic manifestations can also occur from impaired thrombin inhibition.
Medical Science and Discovery · 2014 · 2 citations
A Case Report of Congenital Afibrinogenemia
AbstractCongenital afibrinogenemia is a rare bleeding disorder. It may be manifested as umblical, mucosal, intramuscular, intraarticular, or life-threatening intracranial bleeding. A third-day-old infant was admitted for umblical cord bleeding, and was found to have a prolonged prothrobin time [PT], and activated partial thromboplastin time [aPTT], and a very low fibrinogen level. He was diagnosed as congenital afibrinogenemia, and reported for the rarity of disease, and discussion of novel therapeutic approaches
Pan African Medical Journal · 2016 · 0 citations · open access
Afibrinogénémie congénitale: à propos d’une observation
AbstractAfibrinogenemia is a rare dyscrasia characterized by a congenital fibrinogen deficiency It is transmitted in an autosomal recessive manner. Hemorrhagic manifestations are variable and can be life-threatening. A little more than 250 cases have been published up till now. We here report a new case of congenital afibrinogenemia in a 3 1/2-year old child hospitalized for medium abundance hematemesis. This case study aims to highlight numerous aspects of this condition from a clinical, biological, genetic and therapeutic points of view.
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.
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