DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Takayasu arteritis — screening already-approved drugs against its 22-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTakayasu arteritis maps to a 22-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 takayasu arteritis 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
dual specificity phosphatase 22 (DUSP22) — DUSP22 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 4npdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4WOH · 1.34 Å · ligand 4-NITROPHENYL PHOSPHATE (4NP). Experimental structure, not a prediction.
What the evidence adds up to
From a Japanese national registry analysis of 2,013 patients with Takayasu arteritis, longer disease duration was associated with lower prevalence of active disease symptoms but higher prevalence of organ damage and a greater proportion of patients requiring nursing care. Women tended to have earlier onset and longer disease duration than men; a higher proportion of women had aortic regurgitation and required nursing care. The proportion of female patients in employment was lower than that of the general female population, while no such difference was seen for men. Factors significantly associated with high nursing care needs (level 2 or above, with daily activity limitations) were age at surveillance, brain ischaemia, visual impairment or loss, and ischaemic heart disease.
A 2018 report on rituximab therapy in seven patients with refractory or relapsing Takayasu arteritis found that, despite treatment, four of seven patients experienced persistent disease activity or radiographic disease progression during follow-up. Six of eight patients showed improvement in acute-phase reactant values, and eight of nine were able to reduce daily prednisone dosage. However, only three of seven patients in whom rituximab was used as rescue therapy achieved complete remission. The authors note that in the published literature, only four of nine reported cases had imaging before and after rituximab, and imaging improvement was seen in only two of those four. They conclude that available data are too limited to draw definitive conclusions, though rituximab may be an option in selected refractory cases.
Earlier reviews from 2013 and 2014 describe the established use of steroids and immunosuppressive drugs such as methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, and tacrolimus for active disease. Newer biologic agents including anti-TNF-alpha inhibitors, B-cell depleting agents, and anti-interleukin-6 therapies have been tried in refractory cases with varied success, but experience remains limited. The 2013 review states that identifying the most effective regimens able to control vascular inflammation without undue toxicity remains a challenge, and that validated biomarkers and activity criteria reflecting vascular inflammation are critically needed.
What is still missing are randomised controlled trials to test the efficacy and safety of specific biologic agents such as rituximab, validated biomarkers that correlate with vessel-wall inflammation rather than just systemic inflammatory markers, and imaging-based endpoints that can reliably assess whether treatment is preventing structural damage progression. Without these, the management of Takayasu arteritis will continue to rely on limited evidence and clinical judgement.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Internal Medicine · 1999 · 157 citations
Mycophenolate Mofetil for the Treatment of Takayasu Arteritis: Report of Three Cases
AbstractBACKGROUND: Takayasu arteritis is a rare form of chronic inflammatory disease of the large arterial vessels. Some patients do not respond to steroids or immunosuppressant drugs. OBJECTIVE: To evaluate the effect of mycophenolate mofetil in patients with severe Takayasu arteritis. DESIGN: Case series. SETTING: Clinical Research Center for Rare Diseases in Bergamo, Italy. PATIENTS: Three patients with Takayasu arteritis. INTERVENTION: Mycophenolate mofetil (2 g/d) given orally in two divided doses. MEASUREMENTS: Clinical evaluation and assessment of leukocyte counts were done weekly. Vascular lesions were assessed by using Doppler ultrasonography. RESULTS: All patients showed clinical benefit, and two resumed work after months of inactivity. Patients were also able to taper and discontinue steroid use. Mycophenolate mofetil was well tolerated, and no signs of toxicity were observed. CONCLUSIONS: Mycophenolate mofetil may be an alternative to steroids and cytotoxic agents in patients with Takayasu arteritis. Before results of controlled trials become available, mycophenolate mofetil should be considered only for patients who do not improve or stabilize with conventional therapy.
Circulation Journal · 2023 · 22 citations · open access
Organ Damage and Quality of Life in Takayasu Arteritis ― Evidence From a National Registry Analysis ―
AbstractBACKGROUND: Takayasu arteritis, affecting primarily young women, damages large arteries and organs. We examined the impact of disease duration and sex on organ damage and quality of life using Japan's Intractable Disease Registry. METHODS AND RESULTS: After refining data, 2,013 of 2,795 patients were included in the study. Longer disease duration was related to a lower prevalence of disease activity symptoms, a higher prevalence of organ damage, and a higher proportion of patients requiring nursing care. Compared with men, women tended to have an earlier onset age, exhibiting longer disease duration. A higher proportion of women had aortic regurgitation and required nursing care. The proportion of female patients in employment was lower than that of the general female population, whereas no difference was observed between male patients and the general male population. Logistic regression analysis revealed that age at surveillance, brain ischemia, visual impairment/loss, and ischemic heart disease were significant factors associated with high nursing care needs (Level ≥2, with daily activity limitations). CONCLUSIONS: Early diagnosis and effective treatment, particularly to prevent brain ischemia, visual impairment, and ischemic heart disease, may improve the quality of life of patients with Takayasu arteritis, especially women.
Expert Opinion on Orphan Drugs · 2013 · 20 citations
Management options for Takayasu arteritis
AbstractIntroduction: Takayasu arteritis (TA) is a rare, large vessel vasculitis, which is characterized by substantial morbidity and premature mortality. Several approaches have been used in the recent years for the management of the disease, with some promising results. The best therapeutic strategies still need to be identified. Areas covered: This article discusses the main clinical features of TA and the recent insights into diagnosis and treatments. A search has been undertaken on PubMed and Scopus databases and the most relevant references have been considered. Expert opinion: The identification of the most effective regimens able to control TA unrelenting vascular inflammation without undue toxicity remains a challenge. To define the validated biomarkers and the activity criteria reflecting the specific features of vascular inflammation, and possibly predicting its outcome, represents a critical challenge for physicians in the next years.
AbstractTakayasu arteritis is a well-known rare form of large vessel vasculitis. This review details the clinical features, opportunities of disease activity assessment including new serum biomarkers and imaging diagnostics. Current evidence based treatments are presented and discussed. Particular attention is paid to the effectiveness and complications of interventional and surgical treatment in arteritis Takayasu.
Comment on: Rituximab therapy for Takayasu arteritis: a seven patients experience and a review of the literature: reply
AbstractSir, We read with interest the report by Nakagomi et al. [1] on the results of a multicentric retrospective case series of eight patients with refractory or relapsing Takayasu arteritis (TAK). All but one patient were successfully treated with rituximab (RTX). Disease activity was assessed by Kerr index (National Institutes of Health criteria), laboratory parameters and ability to reduce the daily dose of glucocorticoids. However, radiographic disease activity/progression was not reported. The paper confirms the literature data [2, 3], according to which eight of the nine reported TAK patients responded to RTX therapy with clinical and laboratory remission. However, only in four of these nine cases was imaging reported before and after RTX and imaging improvement was observed in only two cases. In our series, despite RTX therapy, four of seven patients experienced persistent disease activity and/or a radiographic disease progression during follow-up. However, an improvement of acute phase reactant values was observed in six of eight patients and eight of nine patients were able to reduce the daily prednisone dosage. Therefore, although only three of seven patients in whom RTX was employed as rescue therapy achieved complete remission, some improvement in disease activity was observed in most patients. In TAK, disease activity assessed by imaging does not necessarily parallel clinical and laboratory findings. Therefore our different results could be partially explained by the inclusion of imaging monitoring of disease activity before and after RTX in all of our patients. As highlighted by Gonzales-Gay and Castaneda [4] in a recent editorial, the management of patients with TAK is often difficult because the systemic inflammatory response does not always correlate with inflammatory activity in the vessel wall [4, 5]. Persistent disease activity and/or structural damage progression have been reported in patients with normal laboratory tests or clinical remission. The final goal of medical treatment in TAK should be to achieve remission of inflammation in the vessel wall and prevent the progression of structural damage. Therefore imaging modalities are always needed to evaluate the efficacy of therapy in TAK. Until now the available data supporting the use of RTX in TAK patients have been too limited to draw definitive conclusions. However, RTX may represent a therapeutic option in some patients with TAK, especially in selected cases refractory to other immunosuppressive/biologic agents. We agree that a randomized control trial to test the efficacy and safety of RTX in patients with TAK is needed. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: N.P. has been a guest speaker at UCB-sponsored meetings [Immunology Summits, Prague, Czech Republic, 2012, 2013 and 2014; MACRO (Meet the expert at the ACademy of RheumatOlogy), Bologna, Italy, 13–14 April 2012; GRAPPA Workshop, Milan, Italy, 29 January 2016) and an Alfa Wassermann–sponsored meeting (Rhewind, Bologna, Italy, February 2016) and received royalties from Uptodate.com PI for Italy for a gevokizumab in myositis study (Servier 2014), the sirukumab in GCA study (GlaxoSmithKline 2016) and the TOcilizumab in REfractory Myositis (ToReMy) study (Agenzia Italiana del Farmaco 2017) study. All other authors have declared no conflicts of interest.
Journal of Indian College of Cardiology · 2014 · 1 citations
Emerging drug therapies for refractory Takayasu arteritis
AbstractAdequate suppression of the inflammatory process using steroids and immunosuppressive drugs is an established strategy in the treatment of active phase of Takayasu arteritis. Methotrexate, Azathioprine, Cyclophosphamide, Mycophenolate mofetil and Tacrolimus hydrate are generally used as supplement or substitute for steroids to achieve better remission in ‘Refractory Cases’. In recent past newer biologic molecules like Anti-TNF-Alfa inhibitors, B-cell deletion agents, anti-interleukin-6 therapies and Immune-modulating agents have been tried for the management of ‘refractory’ cases with varied success; but the experience is still limited. This is a short review of possible role of each of these novel agents in management of refractory Takayasu arteritis.
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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