DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for vasculitis — screening already-approved drugs against its 27-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleVasculitis maps to a 27-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 vasculitis 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
dihydrofolate reductase (DHFR) — DHFR 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4M6J · 1.201 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2009 cross-sectional study of 86 patients with systemic vasculitis in southern Sweden (46 Wegener’s granulomatosis, 27 microscopic polyangiitis, nine polyarteritis nodosa, four Churg-Strauss syndrome), median Vasculitis Damage Index score was 3 after a median disease duration of 9 years. Only 9% of patients had no damage item. Cardiovascular damage was most common, followed by renal, neuropsychiatric, ear nose and throat, and musculoskeletal damage. Patients with cardiac damage had significantly higher damage rates. Ear nose and throat damage and cardiac or renal damage were almost completely separate: only two of 22 patients with ear nose and throat damage had renal damage, and none had cardiac damage. The authors concluded that damage remains an important problem despite effective remission-inducing drugs.
A 2017 review states that management of systemic vasculitis has been revolutionised by targeted biological agents, but notes the high cost of these agents and the need to ensure optimal utilisation. Goals of therapy include induction and maintenance of remission, preventing relapses, reducing treatment toxicity, and improving quality of life. A 2019 review of systemic necrotizing vasculitides confirms that therapy is dictated by diagnosis, disease extent, and severity. In ANCA-associated vasculitis, induction consists of tapering glucocorticoids combined with specific immunosuppressants; maintenance therapy begins after 3 to 6 months and can require years to prevent relapse. The review mentions that entirely avoiding glucocorticoids may become possible if medications such as avacopan are confirmed safe and effective, but this remains a future possibility.
A 2016 case report describes a 60-year-old woman with propylthiouracil-induced ANCA-associated vasculitis presenting with blood coagulation disorders. After drug withdrawal and steroid use, the patient recovered and then received radioiodine therapy. The authors note that drug-induced vasculitis has a relatively good prognosis, but early diagnosis and timely withdrawal of the causative drug are key. They also acknowledge that the haematologic disorders in this case might have been caused by antibiotics or by the vasculitis itself.
What is still missing: prospective data linking specific damage patterns to long-term outcomes in unselected populations; randomised trials comparing the cost and effectiveness of newer biological agents against standard regimens; and validated strategies for individualising maintenance therapy duration or for safely replacing glucocorticoids with alternatives such as avacopan.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Scandinavian Journal of Rheumatology · 2009 · 33 citations
The extent and pattern of organ damage in small vessel vasculitis measured by the Vasculitis Damage Index (VDI)
AbstractOBJECTIVES: To assess the extent and pattern of irreversible organ damage in patients with Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), polyarteritis nodosa (PAN), and Churg-Strauss syndrome (CSS) by a cross-sectional point prevalence study within a defined geographical area. METHODS: The Vasculitis Damage Index (VDI) was recorded for 86 prevalent cases, classified as 46 patients with WG, 27 with MPA, nine with PAN, and four with CSS from a defined population in southern Sweden, with a median age of 64.8 years and a median disease duration of 9 years. The VDI was determined for all patients at the day of point prevalence (pp), 1 January 2003. RESULTS: The median VDI score was 3 [interquartile range (IQR) 2-5] for all patients: 3 (2-4) for WG, 3 (1.5-4.5) for MPA, 5 (2-6) for PAN, and 1.5 (0.75-2.75) for CSS. Only 9% of patients had not been assigned a single item of damage. The most common damage was cardiovascular, followed by renal, neuropsychiatric, ear nose and throat (ENT), and musculoskeletal. Major vascular and treatment-related damage was associated with advanced age whereas ENT damage was more prevalent in younger patients. There was an almost complete separation between ENT damage and cardiac and renal damage with only two out of the 22 patients assigned ENT damage having experienced renal damage; none had been assigned cardiac damage. Patients with cardiac damage had significantly higher damage rates. CONCLUSIONS: Damage remains an important problem for patients with systemic vasculitis despite effective remission-inducing drugs. Only a small fraction of patients are unmarked by their disease.
Journal of Clinical Pathology · 2017 · 10 citations
Update on systemic vasculitides
AbstractManagement of systemic vasculitis has been revolutionised over the last decade with the introduction of targeted biological agents. With an increase in both the prevalence and the recognition of vasculitis as well as the high cost of these agents, it is important to ensure their most optimal utilisation. The goals of vasculitis therapy include the induction and maintenance of remissions, preventing relapses, reducing the toxicity of therapy with the aim of reducing morbidity and mortality as well as improving the quality of life of those afflicted. This review focuses on the recent advances in the diagnosis, surveillance and treatment of these conditions.
AbstractBACKGROUND: Propylthiouracil is the most common drug used to treat hyperthyroidism. However, this drug could cause a severe disease, antineutrophilic cytoplasmic antibody-associated vasculitis (AAV), which was usually misdiagnosed. METHODS: We reported a 60-year-old woman of propylthiouracil-induced AAV manifested as blood coagulation disorders. The patient was admitted because of hyperthyroidism and leukopenia. At the time of hospitalization, she suffered from dry cough, erythema and knee joints ache, and gradually became febrile. And then BP decreased and PLT was reduced with coagulation disorders. ANCA: c-ANCA positive (1:100), p-ANCA positive (1:320), MPO-IgG positive, PR3-IgG positive, GBM-IgG negative. Erythrocyte sedimentation rate and C-reactive protein increased markedly. Chest high-resolution computed tomography (HRCT) showed that scattered spots, patch and ground-glass opacity. RESULTS: Finally, we made a terminal diagnosis of PTU-induced AAV possibly. After drug withdrawal and use of steroid, the patient recovered well and then accepted RAI therapy. As the patient was given imipenem-cilastatin before the reduction of PLT and coagulation disorders, we considered that the hematologic disorders might be caused by antibiotics or a clinical presentation of the vasculitis itself. CONCLUSION: Drug-induced vasculitis is relatively good prognosis, but early diagnosis and timely withdrawal of associated drugs are the key to the treatment.
Expert Review of Clinical Immunology · 2019 · 6 citations
Treatment of systemic necrotizing vasculitides: recent advances and important clinical considerations
AbstractIntroduction: Primary systemic necrotizing vasculitides (SNVs) include polyarteritis nodosa, Kawasaki disease, ANCA-associated vasculitides, IgA vasculitis, and cryoglobulinemic vasculitis. All are rare but potentially severe, life-threatening conditions. Evidence-based treatments are well established, but continue to evolve and management requires some expertise.Areas covered: The objectives of this review are to outline results of the main recent therapeutic studies for SNV, which have led to the establishment of current treatment strategies and significant improvement in patients’ outcomes, and to describe knowledge gaps that ongoing research hopes to bridge.Expert opinion: Therapy is mainly dictated by diagnosis, disease extent, and severity. In ANCA-associated vasculitis, an initial induction phase consists of tapering glucocorticoids combined with specific immunosuppressants. Maintenance therapy begins after 3 to 6 months, once all evidence of active disease has resolved, and can require years of therapy to prevent relapse. Results from ongoing and future trials for vasculitis will likely impact these treatment approaches. Entirely avoiding GC may become possible, perhaps even the next gold standard, if medications such as avacopan are confirmed to be safe and effective. New combination strategies, more individualized for each patient, may also prove to be more effective, faster.
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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