DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for inflammatory spondylopathy — screening already-approved drugs against its 18-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleInflammatory spondylopathy maps to a 18-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 inflammatory spondylopathy 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
mitogen-activated protein kinase 14 (MAPK14) — MAPK14 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 bogdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3OEF · 1.6 Å · ligand octyl beta-D-glucopyranoside (BOG). Experimental structure, not a prediction.
What the evidence adds up to
The 2012 comparison of European and Latin American ankylosing spondylitis registries included 3,439 patients meeting the modified New York criteria, 2,356 from Europe and 1,083 from Latin America. HLA-B27 prevalence was 83% in the European group and 71% in the Latin American group (p < 0.001). Peripheral arthritis was present in 57% of Latin American patients versus 42% of European patients, and enthesitis in 54% versus 38% (p < 0.001 for both). Treatment differed significantly between populations, with greater use of NSAIDs, corticosteroids, and DMARDs in Latin America, while anti-TNF use and the combination of anti-TNF with methotrexate were more frequent in Europe. The authors concluded that the principal differences were the higher frequency of peripheral arthritis and enthesitis in Latin America, the higher HLA-B27 rate in Europe, and divergent treatment patterns.
A 2005 review reported that etanercept and infliximab were effective in phase III trials for ankylosing spondylitis, and that etanercept, infliximab, and adalimumab safely and effectively relieved signs and symptoms of psoriatic arthritis in phase III trials. Etanercept slowed radiographic progression in psoriatic arthritis, but it was not known whether TNF antagonists could prevent structural damage in ankylosing spondylitis. The same review noted that one trial showed methotrexate might be effective for relieving axial pain in ankylosing spondylitis, but that these findings contradicted two previous studies. For reactive arthritis and undifferentiated spondylarthropathy, a combination of antibiotics was reported as possibly more effective than a single antibiotic for musculoskeletal symptoms.
A 2016 review states that until approximately 2005, treatment options for ankylosing spondylitis were limited to exercise therapy and NSAIDs, and that the introduction of biologic therapies, particularly anti-TNF, transformed pharmacological management of axial spondyloarthritis, especially in severe disease. The TNF inhibitors appear to have a good safety profile in axial spondyloarthritis, with no new safety signals, but the high cost of innovator biologics remains an issue. The same review notes that new therapeutics targeting different cytokine and signalling pathways should become available, but their role remains to be seen. A 2015 review similarly describes pharmacological options as limited until recently, with biological drugs producing remarkable improvements, and notes that physiotherapy and exercise are cost-effective, although home exercise improves some spinal mobility parameters but has no effect on disease activity, pain, stiffness, or global patient evaluation.
The abstracts provide no randomised controlled trial data for any repurposed drug in inflammatory spondylopathy. The only contradictory evidence concerns methotrexate, where one positive trial is offset by two negative studies. What is missing is any trial of a non-biologic, non-NSAID agent with adequate power and long-term follow-up, and any stratification of patients by peripheral versus axial disease, HLA-B27 status, or prior anti-TNF failure. Cost data for biosimilars and comparative effectiveness against existing biologics are also absent from these sources.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Rheumatology · 2012 · 62 citations · open access
Comparison of the Clinical Expression of Patients with Ankylosing Spondylitis from Europe and Latin America
AbstractOBJECTIVE: To compare the clinical, demographic, and serologic characteristics and the treatment of patients diagnosed with ankylosing spondylitis (AS) from Europe (EU) and Latin America (LA). METHODS: We included 3439 patients from national registries: the Spanish Registry of Spondyloarthritis (REGISPONSER), the Belgian registry (ASPECT), and the Latin American Registry of Spondyloarthropathies (RESPONDIA). We selected patients with diagnosis of AS who met the modified New York classification criteria. Demographic, clinical, disease activity, functional, and metrological measurement data were recorded. Current treatment was recorded. The population was classified into 2 groups: patients with disease duration < 10 years and those with disease duration ≥ 10 years. A descriptive and comparative analysis of variables of both groups was carried out. RESULTS: There were 2356 patients in EU group and 1083 in LA group. Prevalence of HLA-B27 was 71% in LA group and 83% in EU group (p < 0.001). We found a greater frequency of peripheral arthritis and enthesitis (p < 0.001) in the LA population; prevalence of arthritis was 57% in LA and 42% in EU, and for enthesitis, 54% and 38%. Except for treatment with anti-tumor necrosis factor (anti-TNF), the use of nonsteroidal antiinflammatory drugs (NSAID), corticosteroids, and disease-modifying antirheumatic drugs (DMARD), and the association of anti-TNF and methotrexate use showed a significant difference (p < 0.001) in the 2 populations. CONCLUSION: The principal differences in the clinical manifestations of patients with AS from EU and LA were the greater frequency of peripheral arthritis and enthesitis in LA group, the higher percentage of HLA-B27 in EU group, and the form of treatment, with a greater use of NSAID, steroids, and DMARD in the LA group.
TURKISH JOURNAL OF MEDICAL SCIENCES · 2015 · 37 citations · open access
Treatment of ankylosing spondylitis
AbstractAnkylosing spondylitis (AS) is a chronic, inflammatory, rheumatic disease involving primarily the spine and sacroiliac joints.It is a prototype of spondyloarthritis (SpA) group diseases and its prevalence in Turkey has been reported as 0.49% (1).It is encountered in mostly young adults and in 80% of the cases symptoms appear before 30 years of age (2).Studies have revealed that the quality of life is reduced and the risk of disability and mortality is increased in patients with AS (3,4).It has been reported that the direct (due to health expenses) and indirect (as a result of workforce loss) economic losses associated with the disease are similar to those of rheumatoid arthritis (RA) in the long term (5).Management of AS consists of pharmacological and nonpharmacological treatment modalities (6-11).The pharmacological treatment options are limited; however, with the recent introduction of biological drugs, remarkable improvements have been reported in this field.In general, the treatment targets include control of symptoms and inflammation (pain, stiffness, and joint swelling), preservation/normalization of physical function, prevention of progressive structural damage and disabilities, and eventually maximizing the longterm health-related quality of life (6,11).The aim of this review article is to present an updated overview of the pharmacologic treatment of AS, as defined by the modified New York criteria (Table 1) (12).Nonpharmacological treatment modalities including physiotherapy and exercise are only briefly mentioned and surgical treatment is not discussed. Nonpharmacological treatment approaches: physiotherapy and exerciseThe nonpharmacological treatment for AS comprises patient training and regular exercise.Pharmacological treatment and nonpharmacological treatment approaches complement each other.Physiotherapy and exercise for the treatment of AS are also cost-effective (13).A recent Cochrane article summarized the available scientific evidence on the effectiveness of physiotherapy interventions in the management of AS ( 14).Personal home exercising and training, when compared to AS patients without such interventions, lead to significant improvement in some spinal mobility parameters (finger tips-to-floor distance); however, they have no effect on disease activity, pain, stiffness, and global patient evaluation (14).Studies comparing group physiotherapy programs applied with a supervisor with personal home exercise programs showed that there were no differences among groups in regard to pain, stiffness, and function; however, some spinal mobility parameters (Schober's distance) and patient global Abstract: Ankylosing spondylitis is a chronic, inflammatory, rheumatic disease that can reduce the quality of life and increase the risk of disability and mortality.It also causes direct and indirect economic losses due to health expenses and as a result of workforce loss.Management of this disease consists of pharmacological and nonpharmacological modalities.Until recently, pharmacological treatment options have been very limited.However, development of novel biological drugs revolutionized the management of this disease.The aim of this review article is to present an updated overview of the pharmacologic treatment of ankylosing spondylitis.Nonpharmacological treatment modalities including physiotherapy and exercise are only briefly mentioned and surgical treatment is not discussed.
Current Opinion in Rheumatology · 2005 · 35 citations
Treatment update on spondyloarthropathy
AbstractPURPOSE OF REVIEW: The unexpected success of the tumor necrosis factor antagonists in ankylosing spondylitis and psoriatic arthritis has generated considerable enthusiasm regarding the therapeutic potential of these drugs. By contrast, concerns regarding the high cost and long-term safety of the tumor necrosis factor blocking agents have prompted investigators to take a closer look at more traditional anti-inflammatory agents and to explore novel therapeutic targets. The purpose of this review is to summarize treatment advances in spondylarthropathy over the past year and to discuss potential future therapies. RECENT FINDINGS: Recent studies indicate that the morbidity of ankylosing spondylitis and PsA are considerably higher than previously reported. Etanercept, infliximab and adalimumab safely and effectively relieved the signs and symptoms of psoriatic arthritis patients in phase III trials. Etanercept and infliximab were also effective in phase III trials in ankylosing spondylitis. Etanercept slowed radiographic progression in psoriatic arthritis trials, but it is not known whether tumor necrosis factor antagonists can prevent structural damage in ankylosing spondylitis. One trial showed that methotrexate may be effective for relieving the pain of axial disease in ankylosing spondylitis but these findings contradict two previous studies. For reactive arthritis and undifferentiated spondylarthropathy, a combination of antibiotics may be more effective than a single antibiotic for the relief of musculoskeletal symptoms. Last, potential therapeutic targets include interleukin-1, interleukin-12, B lymphocytes, accessory molecules on T lymphocytes, and angiogenic factors. SUMMARY: Phase III trials have confirmed that tumor necrosis factor antagonists are effective and safe for the treatment of ankylosing spondylitis and psoriatic arthritis. For patients who do not respond to tumor necrosis factor blockade, several treatment options are under study. Information from these trials will more clearly define the role of disease-modifying antirheumatic drugs, novel therapeutic agents, and antibiotics in the treatment of spondylarthropathy.
AbstractSpondyloarthropathies are important and common inflammatory arthropathies that occur in approximately 2% of the population. They are often underrecognized. The diagnosis features the presence of asymmetrical, predominately lower limb arthritis and/or inflammatory back pain. The spondyloarthropathies can be subdivided into several disease subcategories, including ankylosing spondylitis, Reiter's/reactive arthritis, psoriatic arthritis, inflammatory bowel disease-associated arthritis and a large group of undifferentiated spondyloarthritis. The interactions between infectious agents and the individual's genetic background are important aetiological factors. Therapies for these conditions include physical therapy, non-steroidal anti-inflammatories and disease-modifying drugs.
Oxford University Press eBooks · 2010 · 1 citations
Ankylosing spondylitis, other spondyloarthritides, and related conditions
AbstractThe spondyloarthritides are a group of inflammatory rheumatic diseases with predominant involvement of axial and peripheral joints and entheses, together with other characteristic clinical features, including inflammatory back pain, sacroiliitis, peripheral arthritis (mainly in the legs), enthesitis, dactylitis, preceding infection of the urogenital/gastrointestinal tract, psoriatic skin lesions, Crohn-like gut lesions, anterior uveitis, and a family history of Spondyloarthritis. They are the second most frequent inflammatory rheumatic diseases after rheumatoid arthritis....
Oxford University Press eBooks · 2016 · 0 citations
Drug treatment for axial spondyloarthritis
AbstractThe pharmacological therapy for patients with axial spondyloarthritis (axSpA), especially those with severe disease, has been transformed by the introduction of the biologic therapies, and anti-TNF therapy in particular. Until approximately 2005, treatment options for ankylosing spondylitis (AS) were limited to exercise therapy and non-steroidal anti-inflammatory drugs (NSAIDs). The TNF inhibitors appear to have a good safety profile in axSpA, with no new safety signals. The high cost of innovator biologics remains an issue and it will be interesting to observe the effect of the introduction of multiple biosimilar TNF inhibitors in clinical practice. New therapeutics targeting different cytokine and signalling pathways should also become available over the next few years, so it remains to be seen what their role will be in the management of axSpA. This chapter reviews some of the key drug therapies and advances in the management of axSpA.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
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