DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for rheumatoid arthritis — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRheumatoid arthritis maps to a 46-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 rheumatoid arthritis 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
macrophage migration inhibitory factor (MIF) — MIF 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 ipadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9JIT · 1.08 Å · ligand ISOPROPYL ALCOHOL (IPA). Experimental structure, not a prediction.
What the evidence adds up to
The 2011 review describes advances in understanding rheumatoid arthritis pathophysiology, including the link between the shared epitope, smoking, and anticitrullinated protein/antibody generation, and a hypothesis connecting citrullinating oral bacteria to those antibodies. It notes that TNFα exposure interferes with protein kinase C theta compartmentalisation in regulatory T cells, inhibiting their suppressive function, and that platelet microparticles stimulate fibroblast-like synoviocytes, which may migrate from joint to joint. The 2023 reviews similarly summarise new mechanisms and potential therapeutic targets identified in the preceding year, but provide no concrete efficacy or survival data.
The 2015 review of biologicals states that comparative analyses showed only minor differences in efficacy and safety among established biologicals, and that studies confirmed excellent drug retention, efficacy, and safety for approved biologicals, including in monotherapy. It reports that tapering and sometimes discontinuation of biologicals is possible in disease remission, and that upon relapse, patients usually show full response after reintroduction of the same compound. The 1998 article emphasises that treatment success depends on early intervention and disease modification, with many patients doing well on an individualised regimen including education, rest, diet, exercise, and drug therapy.
No abstract provides quantitative outcomes such as survival or response rates for any specific drug or intervention. The 2000 abstract on a literary work is irrelevant. The 2023 review articles identify new pathogenic mechanisms but do not report trial results. What remains missing are large-scale, randomised controlled trials that test specific repurposed drugs in defined patient subgroups, adequate funding for such trials, and validated biomarkers to stratify patients who might benefit from particular interventions.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Rheumatology · 2011 · 187 citations
Pathophysiology of rheumatoid arthritis
AbstractPURPOSE OF REVIEW: To provide a summary of recent advances in the pathophysiology of rheumatoid arthritis. RECENT FINDINGS: Highlights include further elucidation of the relationship between the shared epitope, smoking and anticitrullinated protein/peptide antibody generation, including identification of putative citrullinated auto-antigens; and a hypothesis linking citrullinating oral bacteria and anticitrullinated protein/peptide antibody generation. Important work on signalling within regulatory T cells has identified sequestration of protein kinase C theta away from the immune synapse as critical for suppressive activity; TNFα exposure interferes with protein kinase C theta compartmentalisation, explaining its inhibition of regulatory T cell function. Platelet microparticles have emerged as important pro-inflammatory mediators via their stimulatory effects on fibroblast-like synoviocytes. The mechanisms by which fibroblast-like synoviocyte invade are becoming elucidated, and recent work suggests the capacity of these cells to migrate from joint to joint, potentially explaining the evolution of clinical rheumatoid arthritis. SUMMARY: Our knowledge of rheumatoid arthritis pathogenesis continues to expand. The last year has seen some key findings, including the identification of novel, potentially tractable targets for further therapeutic research.
Biologicals in rheumatoid arthritis: current and future
AbstractThe aim of the review is to highlight the current knowledge about established and new biologicals and to summarise recent advances by focusing on comparative efficacy, safety and possible discontinuation of treatment in patients with rheumatoid arthritis (RA). Up to now, comparative analyses showed only minor differences with respect to efficacy and safety among the established biologicals. Studies confirmed the excellent drug retention rate as well as efficacy and safety of approved biologicals including their use in monotherapy. Tapering and in some instances discontinuation of biologicals is possible in disease remission. In case of relapse, patients usually show full response after reintroduction of the same compound. The development of biologicals continues fast with several new biologicals targeting different or established cytokines or cellular subsets of the immune system. With several new biologicals in the pipeline and different formulations for established compounds, treatment options for RA will become even more versatile and sophisticated. Although we get closer to the aim of decreasing the proportion of refractory patients, many questions have to be addressed in the near future regarding emerging biosimilars and biologicals with new modes of action.
Clinical and Experimental Rheumatology · 2023 · 27 citations · open access
Pathogenesis of rheumatoid arthritis: one year in review 2023
AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterised by local and systemic inflammation. The complex interplay between immune cells and soluble mediators leads to the induction and perpetuation of aberrant inflammatory and autoimmune responses. The research carried out in the last year in the field of RA enabled the identification of new mechanisms involved in the pathogenesis of the disease and therefore unmasked new potential therapeutic targets. In this review article we summarised the new insights into RA pathogenesis from original research articles published in the last year.
Clinical Drug Investigation · 2021 · 26 citations · open access
Filgotinib in Rheumatoid Arthritis: A Profile of Its Use
AbstractFilgotinib (Jyseleca®), an oral Janus kinase (JAK) inhibitor, is approved as monotherapy or in combination with methotrexate to treat moderate to severe active rheumatoid arthritis (RA) in adults who have an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). In phase 3 trials, once-daily filgotinib was generally well tolerated and associated with an improvement in RA signs and symptoms as well as physical function in patients with an inadequate response to ongoing methotrexate, an inadequate response to ongoing conventional synthetic DMARDs plus an inadequate response or intolerance to prior biologic DMARDs, or limited or no prior exposure to methotrexate. In addition, filgotinib was noninferior to adalimumab in terms of low disease activity response rate (DAS28-CRP ≤ 3.2) in patients with an inadequate response to methotrexate. Filgotinib also appeared to inhibit the radiographic progression of joint damage and led to low disease activity or disease remission (DAS28-CRP < 2.6). Filgotinib showed sustained efficacy, and the safety profile of filgotinib longer term was similar to that in the phase 2 and 3 trials. Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease mainly affecting the small joints of the hands and feet. While there is no cure for RA, biologic disease-modifying antirheumatic drugs (DMARDs), which target the inflammatory cytokines (and their receptors) involved in RA, can achieve low disease activity or disease remission. However, these drugs are not always effective or well tolerated and their administration routes (intravenous or subcutaneous) can be a barrier to use. More recently, oral drugs that act on pathways downstream of cytokine receptors have been developed. These drugs, the Janus kinase (JAK) inhibitors, are targeted synthetic DMARDs. Filgotinib (Jyseleca®), a second-generation JAK inhibitor, improves joint swelling, disease activity, pain, and physical functioning and reduces progression of joint damage in adults with moderate to severe active RA and is generally well tolerated. Like other JAK inhibitors, filgotinib is recommended in treatment guidelines as an effective alternative to biologic DMARDs in adults with moderate to severe active RA who have not responded adequately to or who do not tolerate other DMARDs.
AbstractTreating rheumatoid arthritis can be very satisfying when patients participate fully in designing and implementing their therapeutic strategy. However, the strategy's success depends on early intervention and disease modification. Many patients do well when education, rest, diet, exercise, and drug therapy are incorporated into an individualized regimen.
Espéculo: Revista de Estudios Literarios · 2000 · 1 citations
Realidad y fantasía en Vida de Greta Garbo, de César Muñoz Arconada
AbstractThe mechanisms underlying the pathogenesis of rheumatoid arthritis (RA) involve different components of the immune system. In subjects with genetic predisposition to develop RA, a tight interaction between cells and mediators of the innate and adaptive immune system leads to the amplification and perpetuation of inflammation and tissue remodelling. The research carried out in the last year in the field of RA has improved the current knowledge on the pathogenesis of the disease, and is potentially useful to develop new therapeutic approaches. Thus, in this review we provide an overview on the new insights into RA pathogenesis, resulting from a literature search of the data published in the last year.
Zenodo (CERN European Organization for Nuclear Research) · 2023 · 0 citations · open access
THE PATHOPHYSIOLOGY OF RHEUMATOID ARTHRITIS: ARTICLE REVIEW
AbstractBackground: By delineating the interplay between genetic susceptibility, environmental triggers, and immune dysregulation, this theoretical framework provides a structured understanding of the pathophysiology of rheumatoid arthritis. It is a foundation for investigating potential therapeutic targets and developing interventions that address the intricate molecular and cellular processes involved in RA progression. Objective: As we delve into the depths of RA's pathophysiology, this review aims to synthesize recent findings and seminal contributions, providing a comprehensive overview of the current understanding of the molecular and cellular mechanisms driving this complex autoimmune disorder. By unraveling these intricacies, the contribution to this effort aimed at developing targeted therapeutic interventions and advancing the management of rheumatoid arthritis. Methodology: Comprehensive research of the pathophysiology of rheumatoid arthritis. PUBMED and Google Scholar search engines were the main used databases for the search process, and articles were collected from 1990 to 2023. The terms used in the search were: Rheumatoid arthritis, Pathogenesis, Pathophysiology, Systemic Manifestations. Conclusion: Unraveling the intricate pathophysiology of RA provides a foundation for advancing diagnostic and therapeutic strategies, ultimately improving the quality of life for individuals grappling with this challenging autoimmune disorder. Keywords: Rheumatoid arthritis, Pathogenesis, Pathophysiology, Systemic Manifestations.
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.
