DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for inflammatory bowel disease 19 — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleInflammatory bowel disease 19 maps to a 3-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 bowel disease 19 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
LPS responsive beige-like anchor protein (LRBA) — LRBA 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 1T77 · 2.4 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Inflammatory bowel disease has a strong genetic component, but the mode of inheritance is polygenic and penetrance is heavily influenced by lifestyle in industrialised societies. A 1999 review noted that early linkage studies in affected sibling pairs had identified multiple genomic susceptibility regions, though these regions remained large and no actual disease genes had yet been pinpointed. By 2004, the NOD2 gene (now CARD15) on chromosome 16 had been unequivocally identified as a susceptibility gene for Crohn’s disease, providing proof of principle for positional cloning. Linkage and association studies also gave strong support for susceptibility loci on chromosomes 5q31, 6p21 and 19p, while loci at 3p, 3q and 14q needed further follow-up. Replication of linkage findings had been limited, and the 2004 review noted that important obstacles to further progress remained.
A 2017 study examined IL-19, a member of the IL-10 cytokine family. In biopsies from patients with active ulcerative colitis, IL19 expression was increased compared with patients with quiescent ulcerative colitis. Colitis was attenuated in IL-19–deficient mice, and this attenuation was associated with reduced numbers of IL-6–producing macrophages in the inflamed colonic lamina propria. The authors concluded that microbial-driven expression of IL-19 by intestinal macrophages may contribute to the pathogenesis of inflammatory bowel disease.
A 2024 review described inflammatory bowel disease as incurable and noted that management is not unanimous because patients react differently to the treatment administered. The review brought together various therapeutic targets but did not report any new clinical trial results or concrete response rates. Despite decades of genetic and immunological research, no curative treatment has emerged, and patient responses to existing therapies remain unpredictable. What is still missing is a reliable way to stratify patients by their underlying molecular pathology, and the large-scale, well-funded trials needed to test whether targeting specific pathways—such as IL-19 or NOD2—can produce consistent clinical benefit.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Molecular Genetics · 2004 · 126 citations
Genetics of inflammatory bowel disease: progress and prospects
AbstractStrong epidemiological evidence for a genetic contribution to pathogenesis in inflammatory bowel disease (IBD) has stimulated efforts to identify susceptibility genes for both of its major clinical forms, Crohn's disease and ulcerative colitis. Genome scans for linkage have indicated multiple regions of interest, but replication of these has been limited. The detection of linkage on chromosome 16 (IBD1) led to the unequivocal identification of the NOD2 gene (now called CARD15) as a susceptibility gene for Crohn's disease. This seminal discovery has provided proof of principle for positional cloning and candidate gene approaches to identify IBD genes. It has also led to useful strategic insights in complex disease genetics, and generated new directions in the investigation of the molecular pathways to pathogenesis. Linkage and association studies have also provided strong support for IBD susceptibility genes on chromosomes 5q31, 6p21 and 19p, while loci of interest at 3p, 3q and 14q require further follow-up. Although important obstacles to further progress will need to be overcome, the successes of the past 2 years suggest that a detailed description of the genetic basis of inflammatory bowel disease is a realistic goal.
The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models
AbstractAbstract IL-19, a member of the IL-10 cytokine family that signals through the IL-20 receptor type I (IL-20Rα:IL-20Rβ), is a cytokine whose function is not completely known. In this article, we show that the expression of IL19 in biopsies of patients with active ulcerative colitis was increased compared with patients with quiescent ulcerative colitis and that colitis was attenuated in IL-19–deficient mice. The disruption of the epithelial barrier with dextran sodium sulfate leads to increased IL-19 expression. Attenuated colitis in IL-19–deficient animals was associated with reduced numbers of IL-6–producing macrophages in the inflamed colonic lamina propria. Microbial-driven expression of IL-19 by intestinal macrophages may contribute to the pathogenesis of inflammatory bowel disease.
Current Opinion in Gastroenterology · 1999 · 6 citations
Genetics and inflammatory bowel disease
AbstractGenetic factors have a definite role in the etiology of inflammatory bowel disease (IBD). The mode of inheritance suggests a polygenic disease with the penetrance of the genetic factors being strongly influenced by the lifestyle of an industrialized society. Molecular techniques, which have become available through the progress of the human genome project, allowed a first series of linkage studies in pairs of affected siblings with IBD, which suggested multiple genomic susceptibility regions. These regions are still large, but considerable progress is being made toward the identification of actual disease genes. It is hoped that an understanding of the genetic etiology of IBD will lead to enhanced diagnostic procedures, more effective therapeutic interventions, and preventive strategies in the future.
The American Journal of Gastroenterology · 2010 · 3 citations
NSAIDs and Hormone Replacement Therapy in Geriatric Crohnʼs Disease
AbstractPurpose: The US population is aging and the burden of patients with geriatric Crohn's disease (CD) is increasing. Studies have suggested that inflammatory bowel disease (IBD) including CD in elderly patients is different from the disease in young patients, arguing for two variant disease phenotypes. Treatment patterns may differ between geriatric and young IBD, with elderly patients receiving medications for concomitant illness and prophylaxis of cardiac, vascular and bone health. Nonsteroidal antiinflammatory drugs (NSAIDs) and hormone replacement therapy (HRT) have been associated with initial onset of IBD and reactivation of quiescent disease in IBD. Data describing NSAIDs and HRT treatment in elderly CD is limited. Methods: We performed a comprehensive analysis of CD patients age ≥ 65 followed in a tertiary care center. We determined patterns of CD activity over an 18 month time period and its relationship with treatment patterns of NSAIDs and HRT therapy. CD activity was categorized by retrospective chart review, with active disease defined by physician global assessment, clinical impression, symptoms of diarrhea and abdominal pain, and endoscopic and/or radiographic evidence of activity. Patients were labeled as active disease if they had ≥ 1 relapse during the study period and inactive patients remained in remission the entire time. Results: There were 90 geriatric CD patients, with 35.6% (n = 32) showing evidence of active CD during the study time period. The mean age for active CD was 71.4 ± 6.4 (years ± S.D.) and for inactive CD was 72.8 ± 6.8 (years ± SD). Among geriatric patients with active CD, 9.4% were on NSAIDs while the inactive CD cohort had 15.5% receiving NSAIDs. Female constituted 54% of the geriatric CD patients (n=49) and HRT was identified in only 7 patients (8% of the total and 14% of the female geriatric cohort). Among female CD patients with active disease 19% were on HRT, while 11% of inactive CD geriatric females were on HRT (p=NS). Conclusion: Our study of geriatric CD patients suggests that use of NSAIDs and HRT did not correlate with increased rates of disease activity during an 18 month time period. Further prospective studies evaluating the use of NSAIDs and HRT in geriatric CD are warranted.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
Therapeutic Targets Associated with Medical Research in the Treatment of Inflammatory Bowel Disease
AbstractInflammatory bowel disease (IBD) is a multifactorial disease of the digestive tract. Their prevalence has increased considerably in the previous decade due to industrialization and changes in people's lifestyles. These are incurable diseases whose management is not unanimous because patients react differently to the treatment administered. Therefore, the search for new therapeutic targets is continuous to find better treatment, to reduce the periods of crisis and to improve the health of the patients. In view of this fact, we have in this article brought together the various therapeutic targets associated with these pathologies to produce effective care against inflammatory bowel diseases.
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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