DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for thromboangiitis obliterans — 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 moduleThromboangiitis obliterans 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 thromboangiitis obliterans 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
tumor necrosis factor (TNF) — TNF 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5YOY · 2.727 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 2018 multicentre study of 224 patients with thromboangiitis obliterans, median age at diagnosis was 38.5 years, 23.8% were female, and 81.7% were white. After a mean follow-up of 5.7 years, 58.9% had a vascular event, 21.4% had an amputation, and 1.4% died. The 5-, 10-, and 15-year amputation-free survival was 85%, 74%, and 66% respectively. Non-white ethnicity and limb infection at diagnosis were independent predictors of worse vascular event-free survival. Limb infection at diagnosis carried a hazard ratio of 12.1 for amputation. Patients who stopped tobacco had a lower risk of amputation than those who continued.
A 1949 report from Massachusetts General Hospital described 180 cases over twenty years, with an average of more than four admissions per patient and a total of 24,960 patient days, underscoring the chronicity and economic burden of the disease. A 2019 review states that cigarette smoking is the most important contributing factor and that abstinence from smoking remains the mainstay of treatment. It notes that surgical interventions have minimal scope and that a wide spectrum of medications is available but does not report efficacy data for any drug. The review mentions stem cell therapy as a possible future approach but provides no trial results.
No drug has shown clear efficacy in altering the long-term course of thromboangiitis obliterans in these reports. The 2018 study shows that even with treatment, 34% of patients undergo amputation within 15 years. What is still missing is a randomised controlled trial of any pharmacological agent with amputation or vascular event as the primary endpoint, adequate funding for such a trial, and a reliable method to stratify patients by risk beyond ethnicity and infection status.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of the American Heart Association · 2018 · 72 citations · open access
Long‐Term Outcome and Prognostic Factors of Complications in Thromboangiitis Obliterans (Buerger's Disease): A Multicenter Study of 224 Patients
AbstractBackground Data regarding long-term outcome of patients with thromboangiitis obliterans are lacking and most series come from India and Japan. In this study, we assess long-term outcome and prognostic factors in a large cohort of thromboangiitis obliterans. Methods and Results Retrospective multicenter study of characteristics and outcomes of 224 thromboangiitis obliterans patients fulfilling Papa's criteria were analyzed. Factors associated with vascular events and amputations were identified. The median age at diagnosis was 38.5 (32-46) years, 51 (23.8%) patients were female, and 81.7% were whites. After a mean follow-up of 5.7 years, vascular events were observed in 58.9%, amputations in 21.4%, and death in 1.4%. The 5-, 10-, and 15-year vascular event-free survival and amputation-free survival were 41% and 85%, 23% and 74%, and 19% and 66%, respectively. Ethnic group (nonwhite) (hazard ratio 2.35 [1.30-4.27] P=0.005) and limb infection at diagnosis (hazard ratio 3.29 [1.02-10.6] P=0.045) were independent factors of vascular event-free survival. Factor associated with amputation was limb infection (hazard ratio 12.1 [3.5-42.1], P<0.001). Patients who stopped their tobacco consumption had lower risk of amputation ( P=0.001) than those who continued. Conclusions This nationwide study shows that 34% of thromboangiitis obliterans patients will experience an amputation within 15 years from diagnosis. We identified high-risk patients for vascular complications and amputations.
New England Journal of Medicine · 1949 · 12 citations
Thromboangiitis Obliterans
AbstractTHROMBOANGIITIS obliterans is an uncommon disease. The diagnosis was made at the Massachusetts General Hospital in only 180 cases during the twenty-year period 1926–1945. It makes up for its infrequency, however, by its chronicity, the 180 patients having had a total of 780 different admissions, or an average of over 4 admissions per patient, each one of which averaged thirty-two days or a grand total of 24,960 patient days or sixty-eight-and-one-third patient years. Thus, the problem of therapy is of considerable importance both to the patient and on general economic grounds.The diagnosis of thromboangiitis obliterans at the Massachusetts General . . .
Zenodo (CERN European Organization for Nuclear Research) · 2019 · 0 citations · open access
Thromboangiitis Obliterans (Buerger's Disease)
Abstract<em>Thromboangiitis Obliterans (TAO) is a non-atherosclerotic segmental inflammatory disease predominantly affecting the medium to small sized arteries and veins of both lower and upper extremities. Cigarette smoking is the most important contributing factor in the development of the disease. The disease is assuming alarming proportions on the Indian subcontinent. Clinical features and investigations constitute the basis of an early diagnosis of thromboangiitis obliterans. Abstinence from smoking is the mainstay of treatment despite the availability of a wide spectrum of medications for the treatment of the disease. Surgical interventions have minimal scope in the management of the disease. Newer modalities such as stem cell therapy may perhaps hold a future for preventing disease progression</em>.
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.
