DeCure for Congenital high-molecular-weight kininogen deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital high-molecular-weight kininogen 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 moduleCongenital high-molecular-weight kininogen 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 congenital high-molecular-weight kininogen 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
kininogen 1 (KNG1) — KNG1 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 2-{2-[2-(2-ethoxy-ethoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7QOX · 2.32 Å · ligand 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL (PE4). Experimental structure, not a prediction.
What the evidence adds up to
In four Japanese families with total kininogen deficiency and one with isolated high-molecular-weight kininogen deficiency, immunoblotting with monoclonal antibodies detected no variant kininogen molecule in either condition. Normal plasma showed three bands corresponding to high-molecular-weight kininogen (120,000 and 105,000 apparent molecular weights) and low-molecular-weight kininogen (60,000), and the deficient plasmas simply lacked these bands. No abnormal protein fragments were present.
A separate immunoblotting study compared commercial immunodepleted deficient plasmas with congenital deficiency plasmas. In all congenitally deficient plasmas, high-molecular-weight kininogen remained intact as a single-chain form. In contrast, some artificially depleted plasmas contained proteolytically cleaved, kinin-free kininogen. The degree of cleavage varied by manufacturer; one company’s product contained only trace amounts of cleaved kininogen, while another’s showed complete degradation. The authors propose immunoblot analysis as a quality control method for these commercial products.
A 2019 systematic review of prekallikrein deficiency notes that high-molecular-weight kininogen deficiency is an ultra-rare, autosomal-recessive defect of the contact system caused by biallelic mutations in KNG1. Affected subjects do not manifest a bleeding phenotype. The review describes one new case identified at UMC Mainz and states that a comprehensive individual patient analysis of clinical and diagnostic data is ongoing. No survival or response rates are reported because no treatment trials exist for this condition.
What is still missing: no clinical trial has been conducted for congenital high-molecular-weight kininogen deficiency, and no treatment has been tested. The condition is so rare that no funding body has prioritised a trial, and no patient stratification system has been developed. The natural history remains described only in case series and genetic surveys.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Okayama Igakkai Zasshi (Journal of Okayama Medical Association) · 1990 · 0 citations · open access
Molecular genetic survey of 5 kindreds with kininogen deficiency in Japan
AbstractAnalysis of kininogen molecule status in four Japanese families affected with total kininogen deficiency and one Japanese family with isolated high molecular weight kininogen deficiency was performed using an immuoblotting method with monoclonal antibodies to high molecular weight kininogen (HKG H 12, L 7, L 17).The purified high molecular weight kininogen showed two bands with apparent mot wts of 120, 000 and 105, 000, respectively, and the purified low molecular weight kininogen showed a single band with an apparent mot wt of 60, 000. In normal human plasma, these three bands were also detected. No variant molecule of the kininogens was present in either cases of total kininogen deficiency or isolated high molecular weight kininogen deficiency.
AbstractComparative analysis of high molecular weight kininogen (HK) in various commercial congenital and immunodepleted deficiency plasmas was performed by immunoblotting of HK. It was found, that some artificially depleted deficiency plasmas contained proteolytically cleaved, kinin-free kininogen. In contrast, in all congenitally deficient plasmas, HK was present in the intact, single chain form. Thus, cleavage of kininogen could have been triggered by or during the immunodepletion procedure. It was seen, that the degree of proteolytic cleavage and degradation of HK in depleted plasmas differed among various manufacturers. E.g. depleted products of one company contained only trace amounts of cleaved HK, in contrast to products of another one, in which HK was completely degraded. The immunoblot analysis of HK reflects the occurrence of proteolytic events during the production of artificially deficient plasmas and can therefore serve as a quality control method.
Detection and Differential Diagnosis of Prekallikrein Deficiency: Genetic Study of New Families and Systematic Review of the Literature
AbstractObjectives: Prekallikrein (PK) and high-molecular-weight kininogen (HK) deficiencies are ultra-rare, autosomal-recessive defects of the contact system caused by biallelic mutations in the KLKB1 and KNG1 genes, respectively. Since affected subjects do not manifest a bleeding phenotype, a correct diagnosis is essential to prevent the administration of prohemostatic agents or plasma and to avoid delay of surgery. We describe a new case of PK deficiency identified at UMC Mainz. In addition, we performed a systematic review of the literature to collect blood material for genetic studies of reported PK deficient cases lacking this information, and perform a comprehensive individual patient analysis of clinical and diagnostic data (analysis ongoing).
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.
