DeCure for Hereditary thrombophilia due to congenital protein C deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary thrombophilia due to congenital protein C deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary thrombophilia due to congenital protein C deficiency maps to a 1-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 hereditary thrombophilia due to congenital protein c 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
protein C, inactivator of coagulation factors Va and VIIIa (PROC) — PROC 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 2s,3sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1AUT · 2.8 Å · ligand D-phenylalanyl-N-[(2S,3S)-6-{[amino(iminio)methyl]amino}-1-chloro-2-hydroxyhexan-3-yl]-L-prolinamide (0G6). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary protein C deficiency is an autosomal disorder in which homozygous individuals can have virtually undetectable plasma protein C and fatal massive venous thrombosis shortly after birth, as shown in a family where two infants died and one tested infant had no detectable protein C antigen. Heterozygous family members, aged 4 to 70 years, had reduced protein C levels but no thrombotic episodes in that 1984 report. Later studies confirm that homozygosity and compound heterozygosity are linked to severe early thrombotic complications, while heterozygous patients typically have a moderate form with deep venous thrombosis in adulthood.
Protein C deficiency is an uncommon genetic abnormality that may contribute to thrombophilia, often together with other genetic or acquired risk factors. In the French population, 53 different mutations were found in 90 families. The amount of protein C produced by the mutant allele and the genetic status partly explain the variable clinical expression. Some mutations produce a non-functional circulating protein, mostly in the GLA domain and serine protease domain. The Arg506 to Gln factor V mutation appears in 10 to 20% of symptomatic protein C deficient patients.
A 1998 Korean case reported a 44-year-old woman with recurrent pulmonary thromboembolism who had protein C activity of 35% and antigen of 58%, with the same missense mutation (C6218T) found in asymptomatic family members including her mother, two daughters, and one son. For diagnosis, a functional amidolytic protein C assay should be used for initial testing, and a low level should be confirmed on a new specimen after excluding acquired causes. Antigenic assays can help subclassify the deficiency type. Testing for thrombomodulin and endothelial protein C receptor is not recommended.
No controlled trial has tested any drug specifically for hereditary protein C deficiency. The 2018 case report on oral rehabilitation in thrombophilia with protein C deficiency discusses anticoagulant prophylaxis and hemostasis management during dental procedures, but provides no efficacy data. What is missing is a prospective trial that stratifies patients by mutation type and baseline protein C activity, and that tests whether any intervention reduces thrombotic events without unacceptable bleeding risk.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 1984 · 440 citations
Homozygous Protein C Deficiency Manifested by Massive Venous Thrombosis in the Newborn
AbstractWe studied a family in which two infants had died with massive venous thrombosis shortly after birth. Protein C antigen was undetectable by immunologic assays of plasma available from one infant. (Protein C is a potent naturally occurring anticoagulant that inactivates activated coagulation factors V and VIII). The parents, who were first cousins, both had partial protein C deficiency. Reduced protein C levels were also observed in 12 of 25 additional family members. None of the partially deficient family members (age range 4 to 70 years) had thrombotic episodes. Our data support the view that hereditary protein C deficiency is an autosomal disorder in which the homozygous state may be manifested by the virtual absence of plasma protein C and by fatal thrombosis in the neonatal period.
Archives of Pathology & Laboratory Medicine · 2002 · 86 citations
Laboratory Issues in Diagnosing Abnormalities of Protein C, Thrombomodulin, and Endothelial Cell Protein C Receptor
AbstractAbstract Objective. —To review the current understanding of the pathophysiology of protein C deficiency and its role in congenital thrombophilia. Recommendations for diagnostic testing for protein C function and concentration, derived from the medical literature and consensus opinions of recognized experts in the field, are included, specifying whom, how, and when to test. The role of related proteins, such as thrombomodulin and endothelial protein C receptor, is also reviewed. Data Sources. —Review of the published medical literature. Data Extraction and Synthesis. —A summary of the medical literature and proposed testing recommendations were prepared and presented at the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. After discussion at the conference, consensus recommendations presented in this manuscript were accepted after a two-thirds majority vote by the participants. Conclusions. —Protein C deficiency is an uncommon genetic abnormality that may be a contributing cause of thrombophilia, often in conjunction with other genetic or acquired risk factors. When assay of protein C plasma levels is included in the laboratory evaluation of thrombophilia, a functional amidolytic protein C assay should be used for initial testing. The diagnosis of protein C deficiency should be established only after other acquired causes of protein C deficiency are excluded. A low protein C level should be confirmed with a subsequent assay on a new specimen. Antigenic protein C assays may be of benefit in subclassification of the type of protein C deficiency. The role of thrombomodulin and endothelial cell protein C receptor in thrombosis has yet to be clearly established, and diagnostic testing is not recommended at this time.
Molecular Basis For Protein C Hereditary Deficiency
AbstractThe clinical presentation of hereditary protein C deficiency is highly variable. Homozygosity and compound heterozygosity have been linked to severe thrombotic complications early in the life. Heterozygous patients have a moderate form of the disease with deep venous thrombosis during adulthood. In the French population, we found 53 different mutations in 90 families. The amount of the protein C produced by the mutant allele as well as the genetic status partly account for the variable clinical expression. Other gene may also be involved: Arg 506 to Gln factor V mutation shows a frequency of 10 to 20% in symptomatic protein C deficient patients. Some protein C gene mutations are associated with a non functional circulating protein; most of them are located in the GLA domain and in the serine protease domain. The biochemical characterization of a few of theses variants has shown the important role of some amino acids on the activation and the mechanism of action of protein C.
Journal of Korean Medical Science · 1998 · 4 citations · open access
Hereditary protein C deficiency with recurrent thrombosis: identification of a missense mutation (C6218T)
AbstractProtein C is the central component of a major anti-thrombotic regulatory system and individuals with hereditary protein C deficiency (PCD) tend to have an increased risk of thromboembolism. During the last several years, mutations causing PCD have been identified in Western countries and in Japanese. In the present study, we report a case of hereditary PCD with a missense mutation (C6218T) in a 44 year old female with recurrent pulmonary thromboembolism. The protein C activity (35%) and antigen (58%) levels in this patient were decreased. Furthermore, we have identified the same molecular defect and PCD in other asymptomatic family members including proband's mother and two daughters and one son. To our knowledge, this is the first case of hereditary PCD with identified genetic defect in the Korean population, which may be one of hot spots for mutation in the protein C gene.
International Journal of Medical and Surgical Sciences · 2018 · 0 citations · open access
Therapeutic Approach in Oral Rehabilitation of Patients Diagnosed with Thrombophilia, Protein C Deficiency
AbstractThrombophilia is defined as any alteration, either congenital or acquired, which promotes and/or facilitates the presentation of a thrombotic phenomenon. Drug treatment of this condition is to prevent (prophylaxis) other thrombotic event by anticoagulant therapy and hemostasis is affected, taking this great implication in the therapeutic approach in oral rehabilitation, leaning realize treatments with prosthetic structures on implants, teeth or tissue-borne. The aim of this case report is to present therapeutic alternatives in patients diagnosed with thrombophilia with protein C deficiency.
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.
