DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for platelet-type bleeding disorder 19 — 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 modulePlatelet-type bleeding disorder 19 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 platelet-type bleeding disorder 19 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
glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) — GNE 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 udpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4ZHT · 2.69 Å · ligand URIDINE-5'-DIPHOSPHATE (UDP). Experimental structure, not a prediction.
What the evidence adds up to
The 2007 review of immune thrombocytopenic purpura in adults states that most patients have a generally well tolerated disease with little morbidity. Splenectomy is described as the best curative treatment for adults with chronic disease of at least six months follow up. Treatments such as anti-D, rituximab or dexamethasone may allow splenectomy to be postponed, possibly indefinitely, if a haemostatic platelet count is attained. Mortality from bleeding may be relevant only in patients refractory to splenectomy. Cytotoxic agents should be reserved for patients with bleeding refractory to other treatments. The review recommends treatment for patients with platelet counts below 30 x 10⁹/L or bleeding, but notes that an aggressive approach is justified only in patients with platelet counts below 20 x 10⁹/L and those refractory to splenectomy.
The 1992 clinical review of platelet function defects states that hereditary storage pool disease is common enough to be suspected in a child with characteristic findings, while acquired defects, especially from drugs, are very common. The template bleeding time is generally useful as a screening test, but a normal result in the presence of a suggestive history or frank bleeding is not reliable. The mainstay of therapy for significant bleeding is liberal infusion of platelet concentrates. For acquired defects, the review recommends treating or controlling the underlying disease and discontinuing offending drugs.
The 2014 study of 19 patients with Glanzmann thrombasthenia identified homozygous or compound heterozygous mutations in ITGA2B or ITGB3 in 16 patients, with 27 different mutations found, 17 of which were novel. Three patients had no detectable molecular genetic anomalies in these genes. Bleeding signs included epistaxis, mucocutaneous bleeding, haematomas, petechiae, gastrointestinal bleeding, and menorrhagia. The 2021 study of 49 patients with acute intracranial haemorrhage found clinically relevant platelet dysfunction in 14 patients (29%). Of those, 8 were on antiaggregatory medication, and 6 patients (12%) were diagnosed with acute acquired platelet dysfunction without such medication.
The 2004 study evaluated the Cone and Plate(let) Analyzer in 165 consecutive bleeding patients and 54 healthy controls. Among 43 patients diagnosed with platelet adrenergic receptor dysfunction, surface coverage was significantly lower (6.2±2.4%) compared to other patients (11.5±3.4%) or healthy controls (12.3±3.0%). In a modified CPA test with epinephrine pre-incubation, surface coverage declined by 73% in healthy controls but only 15% in patients. Seventeen patients with adrenergic receptor dysfunction underwent surgery after DDAVP; surface coverage values followed VWF:RCo levels, and all operations were successful without excessive bleeding. The study notes that routine aggregometry did not show a change in response to epinephrine after DDAVP. What remains missing for platelet-type bleeding disorder 19 specifically is any dedicated trial, any validated diagnostic criteria that distinguish it from other platelet disorders, any patient stratification by genotype, and any funding for a prospective study of its natural history or response to existing therapies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Hematology · 2007 · 86 citations
Immune thrombocytopenic purpura in adults
AbstractPURPOSE OF REVIEW: A review of recent studies was conducted to determine if guidelines promulgated by the American Society of Hematology and the British Committee for Standards in Haematology need to be updated as these were based mainly on expert opinion rather than outcomes derived from clinical trials. RECENT FINDINGS: Recent studies suggest that most patients with immune thrombocytopenic purpura have a disease that is generally well tolerated, with little morbidity. Splenectomy remains the best 'curative' treatment for adults with chronic disease (at least 6 months of follow up). Other treatments such as anti-D, rituximab or dexamethasone may allow the decision of splenectomy to be postponed, possibly indefinitely, if hemostatic platelet count is attained. Mortality from bleeding may be relevant only in patients refractory to splenectomy. Cytotoxic agents should be reserved for patients with bleeding refractory to other treatments. SUMMARY: Patients with platelet counts less than 30 x 10(9)/l or bleeding have to be treated but management decisions should also be based on lifestyle, age, and other medical conditions that may contribute to the risk of serious bleeding. An aggressive therapeutic approach is justified only in patients with platelet counts below 20 x 10(9)/l and those refractory to splenectomy. Newer therapies may be more targeted in their action.
Seminars in Thrombosis and Hemostasis · 1992 · 38 citations
Platelet Function Defects: A Clinical Review
AbstractPlatelet dysfunction, especially acquired forms, are common causes of hemorrhage, especially in association with trauma and surgery. Although the hereditary platelet function defects are generally quite rare, hereditary storage pool disease is common enough to be suspected in an individual, usually a child, with characteristic historical and clinical findings. The acquired platelet function defects, especially those resulting from drugs, are very common and should promptly be suspected in patients developing easy and spontaneous bruising, mild to moderate mucosal membrane hemorrhage, or unexplained bleeding associated with trauma or surgery. The template bleeding time is generally useful as a screening test of platelet function, but a normal template bleeding time, in the presence of a suggestive history, suggestive clinical findings, or in the patient frankly bleeding, is not reliable and platelet aggregation or lumi-aggregation should be done in appropriate clinical situations. The mainstay of therapy for essentially all these defects, if bleeding is significant, is the liberal infusion of appropriate numbers of platelet concentrates. The acquired platelet function defects, of course, should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should promptly be discontinued.
Characterisation of patients with Glanzmann thrombasthenia and identification of 17 novel mutations
AbstractGlanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterised by quantitative and/or qualitative defects of the platelet glycoprotein (GP) IIb/IIIa complex, also called integrin αIIbβ3. αIIbβ3 is well known as a platelet fibrinogen receptor and mediates platelet aggregation, firm adhesion, and spreading. This study describes the molecular genetic analyses of 19 patients with GT who were diagnosed on the basis of clinical parameters and platelet analyses. The patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, gastrointestinal bleeding, and menorrhagia. Homozygous or compound heterozygous mutations in ITGA2B or ITGB3 were identified as causing GT by sequencing of genomic DNA. All exons including exon/intron boundaries of both genes were analysed. In a patient with an intronic mutation, splicing of mRNA was analysed using reverse transcriptase (RT)-PCR of platelet-derived RNA. In short, 16 of 19 patients revealed 27 different mutations (ITGA2B: n=17, ITGB3: n=10). Seventeen of these mutations have not been published to date. Mutations in ITGA2B or ITGB3 were identified as causing GT in 16 patients. We detected a total of 27 mutations in ITGA2B and ITGB3 including 17 novel missense, nonsense, frameshift and splice site mutations. In addition, three patients revealed no molecular genetic anomalies in ITGA2B or ITGB3 that could explain the suspected diagnosis of GT. We assume that these patients may harbour defects in a regulatory element affecting the transcription of these genes, or other proteins may exist that are important for activating the αIIbβ3 complex that may be affected.
Reduced Platelet Activity in Patients with Acute Intracranial Hemorrhage
AbstractBACKGROUND: Acquired platelet dysfunction is a common element of trauma-induced coagulopathy and has been linked to increased mortality. The aim of the study was to describe the prevalence of platelet dysfunction in patients with acute intracranial bleeding. METHODS: Patients diagnosed with acute intracranial bleeding were screened for eligibility. Patients with an urgent need for craniotomy were enrolled in this prospective monocentric study. Platelet function analyses using multiple electrode aggregometry (TRAPtest, ASPItest and ADPtest) and conventional coagulation tests were performed. The area under the aggregation curves of the ASPItest and ADPtest were defined as primary outcome variables. RESULTS: Seventy-seven patients were screened for eligibility, and 49 patients were ultimately enrolled in the study. In 14 patients (29%), clinically relevant platelet dysfunction was observed. Of those, 8 patients were treated with antiaggregatory medication at the time of study inclusion. Six patients (12%) were diagnosed with acute acquired platelet dysfunction. CONCLUSIONS: Decreased platelet function was present in nearly one-third of patients with acute intracranial bleeding. Hemotherapy algorithms for the treatment of coagulopathy in this cohort should incorporate aggregometric measures to enable rapid goal-directed therapy.
Platelet Adrenergic Receptor Dysfunction Is Associated with Both Aggregation and Adhesion Defects: Application of the Cone and Plate(let) Analyzer for Diagnosis and Monitoring of the Response to DDAVP Therapy.
AbstractAbstract Diagnosis of platelet function disorders is based on the nature of bleeding symptoms, a positive family history and abnormal laboratory tests. However, currently available methods are time and labour consuming and lack sensitivity and specificity. In the present study we evaluated the performance of the Cone and Plate (let) analyzer (CPA) for screening patients with a suspected platelet function disorder and for monitoring therapy. Consecutive patients presenting with spontaneous or post surgical bleeding were studied. All patients underwent primary and secondary hemostasis evaluation including CPA testing. In this test a volume of 200μL of citrated whole blood is placed onto polystyrene wells and submitted to flow (shear rate of 1800 sec. −1) by a Teflon cone for 2 minutes. The resulting platelet deposition is then read by an image analyzer and expressed as % of the well surface covered ( SC, %) with adhered platelets and as the average size (AS, μm2)of platelet aggregates. Patients with a platelet function disorder were further tested with a modified CPA test in which blood samples are pre-incubated (1 min.) with a sub-optimal concentration of an agonist prior to subjecting the sample to the regular CPA test. Response of platelets to the agonist leads to agglutination and micro aggregates formation in the suspension phase of the test tube with consequent decline in platelet adhesion. 165 consecutive bleeding patients were evaluated and compared to 54 healthy controls. We diagnosed 51 patients as suffering from a platelet function disorder, of whom 8 patients (GTA – 7, BSS – 1) were excluded. The remaining 43 patients presented complete unresponsiveness to epinephrine in repeated platelet aggregation tests while all other coagulation, liver and renal function tests were normal and similar to healthy controls. In the CPA test these 43 patients had a significantly lower SC values compared to the other patients or to healthy controls. To further explore the CPA’s diagnostic capability 6 patients were compared to 16 randomly chosen controls using the modified CPA test. Whereas SC declined significantly by 73% in healthy controls after pre-incubation with epinephrine a non significant decline of only 15% was noted in patients with platelet adrenergic receptor dysfunction (table). Seventeen patients with platelet adrenergic receptor dysfunction underwent surgery. Following pre-surgical administration of DDAVP SC values followed closely and the VWF:RCo levels whereas the response to epinephrine in routine aggregometry did not change. All patients underwent successful operations without excessive bleeding. Our data suggest that patients with adrenergic receptor dysfunction suffer from a combined aggregation and adhesion platelet defects. The CPA test was found useful for screening both adhesion and aggregation of platelet disorders including adrenergic receptor dysfunction as well as for monitoring DDAVP therapy in these patients. Adrenergic receptor dysfunction No disorder Healthy controls * max. response to epinephrine in aggregometry ** 1 min. incubation with epinephrine N 43 114 54 Bleeding time (min.) 5.6±2.5 5.5±2.3 6.7±3.1 Aggregomatry * 23% 82% 81% SC% 6.2±2.4 11.5±3.4 12.3±3.0 Modifioed CPA-pre 6.5±2.2 9.4±1.8 Modified CPA-post** 5.4±1.3 2.5±0.8
[Myelodysplastic syndrome with refractory hemorrhage due to reduced platelet aggregation activity].
AbstractA 75-year-old woman suffered a cat bite 10 months after myelodysplastic syndrome (MDS) diagnosis. She visited our hospital because the internal bleeding of the wound did not improve. Although the wound was treated, the bleeding did not stop. She was hospitalized for emergency medical treatment because the bleeding volume exceeded 200 ml. Although her platelet count was normal, the platelet function test showed a decrease in collagen and arachidonic acid aggregation. After platelet transfusion, her bleeding stopped. Patients with MDS may potentially have platelet dysfunction. In the case of bleeding without thrombocytopenia, a platelet function test should be performed and treatment intervention, such as platelet transfusion, should be considered.
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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