DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hemophilia A — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHemophilia A maps to a 10-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 hemophilia a 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 VII (F7) — F7 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 2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5PAG · 1.36 Å · ligand (2R)-2-hydroxy-N-[[3-[5-hydroxy-4-(1H-pyrrolo[3,2-c]pyridin-2-yl)pyrazol-1-yl]phenyl]methyl]-3-methylbutanamide (7YJ). Experimental structure, not a prediction.
What the evidence adds up to
A 2010 review of gene therapy for haemophilia A and B noted that hepatic delivery using adeno-associated virus vectors produced therapeutic but transient clotting factor IX levels in severe haemophilia B patients. T-cell-mediated immune responses eliminated the transduced hepatocytes, though transient immunosuppression was suggested as a possible workaround. Lentiviral vectors and nonviral transposon-based vectors showed sustained correction in rodent models, but the review stressed that translational studies in large animals were still needed before those approaches could move into the clinic.
A 2021 review of emerging drugs for haemophilia A summarised current pharmacological approaches including plasma-derived and recombinant factor VIII products, extended half-life factor VIII products, bypassing agents, and non-replacement therapies. The review stated that novel therapies were already changing management and predicted that as more therapies gained approval there would be a revolution in management, but also noted that clinicians would face challenges incorporating new technologies into practice. No specific response rates, survival figures, or sample sizes from phase II or III trials were given in that review.
A 2012 genetic study, the Hemophilia Inhibitor Genetics Study Combined Cohort, analysed 833 subjects from three independent cohorts, including 104 brother pairs discordant for inhibitor status. After typing 13,331 single-nucleotide polymorphisms from 1,081 immune-related genes, 53 markers were found to be significant predictors of inhibitor status after adjustment for confounders, with 13 having a meta p-value below 0.001. Eight of the 53 markers were significant predictors among the discordant pairs. The authors concluded that the results supported the complexity of the immune response and called for further research into the pathways involved.
What is still missing is a gene therapy approach that achieves durable, clinically meaningful factor expression without being eliminated by the immune system, and large-scale randomised trials that report concrete efficacy and safety outcomes for the newer drugs. The genetic work identifies candidate markers but does not yet provide a clinically actionable stratification tool for inhibitor 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.
Blood · 2012 · 104 citations
The polygenic nature of inhibitors in hemophilia A: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort
AbstractStudies of determinants of development of inhibitory Abs to factor VIII in people with hemophilia A indicate a complex process involving multiple factors. The Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort was formed to extend our understanding of the genetic background of risk. The study group contains 833 subjects from 3 independent cohorts: brother pairs and singletons with and without a history of inhibitors, as well as 104 brother pairs discordant for inhibitor status. Using an Illumina iSelect platform, 13 331 single-nucleotide polymorphisms from 1081 genes, primarily immune response and immune modifier genes, were typed. Each cohort was analyzed separately with results combined using a meta-analytic technique. After adjustment for potential confounders, 53 single-nucleotide polymorphisms were found to be significant predictors of inhibitor status using the criteria of odds ratios in the same direction in all cohorts or allowing for a 20% interval around an odds ratio = 1 in 1 of the 3 and significant in at least 2. Of the 53 markers, 13 had meta P < .001. Eight of the 53 were significant predictors among the discordant pairs. Results support the complexity of the immune response and encourage further research with the goal of understanding the pathways involved.
Current Opinion in Hematology · 2010 · 29 citations
Preclinical and clinical progress in hemophilia gene therapy
AbstractPURPOSE OF REVIEW: Hemophilia A and B are attractive target diseases for gene therapy, as stable expression of coagulation factor VIII and IX may correct the bleeding diathesis. This review focuses on the recent progress in preclinical and clinical studies in gene therapy for hemophilia A and B. RECENT FINDINGS: Hepatic gene delivery using vectors derived from adeno-associated virus (AAV) resulted in therapeutic but transient functional clotting factor IX (FIX) expression levels in severe hemophilia B patients. Although T-cell-mediated immune responses eliminated the transduced hepatocytes, transient immunosuppression may potentially overcome this limitation. Alternatively, vectors are being developed that result in higher FIX expression levels at lower vector doses. Lentiviral vectors are being explored for in-vivo hepatic gene delivery and for ex-vivo transduction of hematopoietic stem cells. This resulted in stable correction of the bleeding diathesis in hemophilic mice. Finally, nonviral vectors derived from transposons result in sustained clotting-factor expression in rodent models. Translational studies in large animal models are required to move these new approaches forward into the clinic. SUMMARY: New insights from clinical trials and advances in preclinical studies may ultimately pave the way toward a cure in patients suffering from hemophilia.
Expert Opinion on Emerging Drugs · 2021 · 2 citations
Emerging drugs for hemophilia A: insights into phase II and III clinical trials
AbstractINTRODUCTION: Hemophilia is a lifelong, genetic-bleeding disorder, which inadequately treated results in permanent joint damage. It is characterized by spontaneous and trauma-related bleeding episodes. In the last 50 years, treatment has seen dramatic improvements which have improved the quality of life of persons with hemophilia. AREAS COVERED: This review will provide a summary of current pharmacological approaches for hemophilia A as well as discuss novel agents which are either approved recently or in phase II-III clinical trials, plasma-derived and recombinant factor VIII (FVIII) products, extended half-life FVIII products, bypassing agents and non-replacement therapies. EXPERT OPINION: Novel therapies are already changing the way that hemophilia A is managed, and as more new therapies get approved, there will be a revolution in the management of this serious condition. Clinicians will have both the opportunities as well as the challenges of incorporating such new technologies into clinical practice.
Journal of Thrombosis and Haemostasis · 2025 · 1 citations · open access
A repeated time-to-event model for personalized treatment of patients with hemophilia A based on individual bleeding risk
AbstractBACKGROUND: Pharmacokinetic-guided dosing of factor (F)VIII concentrates is widely recommended to personalize the treatment of patients with hemophilia A. However, it is well known that commonly applied target FVIII plasma levels do not necessarily improve bleeding outcomes in all individuals. It is therefore desirable to adapt treatment based on individual bleeding risk rather than only factor levels. Unfortunately, there is currently no reliable clinical marker that reliably differentiates between patients with low or high-bleeding risk. OBJECTIVES: We explore the possibility of using repeated time-to-event models to quantify individual bleeding risk by combining (historical) information on annual bleeding rates and pharmacokinetics, without requiring the measurement of novel clinical markers. METHODS: We improved upon existing repeated time-to-event models using data from 264 patients with severe hemophilia A followed during 3 clinical trials. The model classified patients into low-bleeding, medium-bleeding, or high-bleeding frequency cohorts to reduce between-patient variability and predicted bleeding risk for specific categories of bleeds rather than pooled bleeding information. RESULTS: The resulting model has high accuracy, with >70% of predictions being within 1 bleed of the true observed bleeding rate. We demonstrate how the proposed model can be used to compare treatment based on not only the achievement of specific factor levels and factor concentrate consumption but also on projected bleeding outcomes. Importantly, this approach does not require the measurement of novel or unconventional biomarkers, facilitating its adoption in routine clinical practice. CONCLUSION: The proposed method may present an exciting new treatment paradigm for patients with hemophilia A.
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.
