DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for Crohn's disease — screening already-approved drugs against its 39-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCrohn's disease maps to a 39-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 crohn's disease 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
autophagy related 16 like 1 (ATG16L1) — ATG16L1 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 r,rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5NUV · 1.55 Å · ligand (R,R)-2,3-BUTANEDIOL (BU3). Experimental structure, not a prediction.
What the evidence adds up to
A 1986 review states that prednisone remains the mainstay of Crohn’s disease treatment. A substantial fraction of steroid-treated patients are refractory to therapy; adding azathioprine or methotrexate has a corticosteroid-sparing effect and increases duration of remission. Controlled ileal release budesonide (9 mg daily) induces clinical remission in 60–70% of patients with Crohn’s ileitis or right-sided colitis, but continued budesonide treatment has only a finite effect on remission duration. The efficacy of mesalazine in active disease is limited and requires high doses (4000 mg/day); its role in remission is disputed, and there is no evidence of a corticosteroid-sparing effect.
A 2022 commentary reports that biologics produce temporary remissions in 40% of cases and have yet to induce permanent remissions. The author argues that the FDA’s reliance on comparative, placebo-controlled, double-blinded studies has created an impediment to acceptance of divergent alternative therapies, effectively surrendering the therapeutic dialogue to those who can pay for such studies.
Two gene-expression studies from 2008 and 2010 identified potential biomarkers but no drug targets. The 2010 study compared genome-wide transcription profiles of circulating leukocytes in patients with active and quiescent Crohn’s disease and found complex changes, with inflammatory molecules overexpressed or underexpressed in active disease. The 2008 study analysed five mucosal transcripts (aldolase B, elafin, MST-1, simNIPhom, SLC6A14) in 23 Crohn’s patients and 67 controls. In noninflamed rectal mucosa, aldolase B, elafin, simNIPhom and SLC6A14 were increased, while MST-1 was decreased. In inflamed colonic mucosa, aldolase B was increased and elafin and simNIPhom were decreased. No correlation was detected between clinical activity (Mayo score ≤5 vs. ≥6) and transcript expression.
What is still missing is a trial design that can test alternative therapies outside the current regulatory framework, and patient stratification based on the gene-expression patterns described. No drug mentioned in these abstracts has been shown to cure Crohn’s disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Gastroenterology · 2010 · 19 citations
Differential Regulation of Peripheral Leukocyte Genes in Patients With Active Crohn's Disease and Crohn's Disease in Remission
AbstractGOALS: Assessment of disease severity is a frequent challenge in the management of Crohn's disease. Noninvasive, accurate markers for monitoring disease activity are urgently required. Specific gene expression patterns and molecular biomarkers associated with active Crohn's disease could serve as such markers, thereby providing a novel approach to disease activity monitoring. BACKGROUND: Gene expression profiling in circulating leukocytes has shown promise in several medical conditions and blood may provide an easily accessible surrogate tissue for using gene expression profiling to assess activity of Crohn's disease. STUDY: In this study, we compared genome-wide transcription profiles of circulating leukocytes in patients with active and quiescent Crohn's disease. RESULTS: We observed complex changes in blood gene expression patterns in active Crohn's disease: genes of various functional categories were differentially regulated between active and inactive Crohn's disease. We specifically identified a number of inflammatory molecules overexpressed or underexpressed in active Crohn's disease and validated a subset of these genes by real-time reverse transcription-polymerase chain reaction. CONCLUSIONS: The genes differentially regulated in peripheral leukocytes represent potential new biomarkers for assessing the activity of Crohn's disease.
European Journal of Gastroenterology & Hepatology · 2008 · 16 citations
Real-time PCR quantification analysis of five mucosal transcripts in patients with Crohnʼs disease
AbstractOBJECTIVES: Crohn's disease has a genetic background. Onset of the clinical manifestations, however, is suggested to be triggered by environmental factors. Microarray analysis has shown that the expression of transcripts aldolase B, elafin, MST-1, simNIPhom and SLC6A14 are altered in patients with ulcerative colitis. The primary aim of this study was to explore the expressions of these five transcripts in macroscopically inflamed and noninflamed mucosa in patients with Crohn's disease. METHODS: Mucosal specimens obtained from colon in consecutive patients with Crohn's disease (n=23) and controls (n=67) undergoing colonoscopy were analyzed using real-time PCR technique. RESULTS: The expressions of the transcripts aldolase B, elafin, simNIPhom and SLC6A14 were increased, whereas the expression of MST-1 was decreased in noninflamed rectal mucosa in patients with Crohn's disease compared with controls. The expression of aldolase B was increased and the expressions of elafin and simNIPhom were decreased in inflamed colonic mucosa compared with noninflamed rectal mucosa in patients with Crohn's disease. No correlation, between the clinical activity of Crohn's disease (Mayo score <or=5 vs. >or=6) and transcript expression was detected. CONCLUSION: The mucosal transcript pattern in Crohn's disease may, based on the known biological function of the transcripts, explain some of the typical features of Crohn's disease and indicate a possible pathophysiological role of microbes. Our results may thereby contribute to the understanding of the pathogenesis and manifestations of Crohn's disease.
Therapy of Mild to Moderate Luminal Crohn’s Disease
AbstractThe management of luminal Crohn's disease, the most common form of initial presentation of the disease, depends on the location and the severity of the lesions. Mild to moderate disease represents a relatively large proportion of patients with a first flare of luminal disease, which may also be associated with perianal disease. As quality of life of these patients correlates with disease activity, adequate therapy is a central goal of the overall patient management. Treatment options include mainly sulfasalazine, budesonide and systemic steroids, while the role of mesalazine and antibiotics remains controversial. The role of biological therapies in mild to moderate disease has not been thoroughly evaluated and will not be discussed here.
Journal of Clinical Pathology · 2022 · 11 citations
Dasatinib-induced Crohn’s-like colitis
AbstractDasatinib is a second-generation multityrosine kinase inhibitor used in the first-line and second-line treatment of Philadelphia chromosome-positive leukaemia. The most frequent type of Dasatinib-induced intestinal injury is haemorrhagic colitis; other morphologic patterns include apoptotic colopathy, CD8+ T-cell-mediated colitis and non-specific colitis. Aim of this study is to describe a novel Crohn's-like histopathologic pattern of Dasatinib-induced colitis. Four patients developed diarrhoea during Dasatinib treatment; colonoscopy was performed and biopsy sets were taken for histological analysis. All patients showed patchy, chronic active inflammation with cryptitis and microgranulomas (two patients). Ileal and rectal biopsies showed either no or mild, focal inflammation. An increase in lamina propria eosinophils was seen (two patients) and apoptoses were seen (three patients). Complete remission was observed after interruption of treatment. Dasatinib-induced colitis and Crohn's disease may share histologic features including microgranulomas, which can potentially lead to misdiagnosis if no information on treatment is provided.
Drug and Therapeutics Bulletin · 1986 · 10 citations
The drug treatment of crohn’s disease
AbstractThe medical management of Crohn's disease has changed in recent years, but the mainstay of treatment is still prednisone. A substantial fraction of steroid-treated patients are refractory to therapy and addition of azathioprine or methotrexate has a corticosteroid-sparing effect and increases duration of remission. Controlled ileal release budesonide (9 mg daily) induces clinical remission in 60-70% of patients with Crohn's ileitis or right-sided colitis, and continued budesonide treatment has a finite effect on the duration of remission. The efficacy of mesalazine in active Crohn's disease is limited and high doses are required (4000 mg/day). The role of mesalazine in Crohn's disease in remission is disputed, and there is no evidence of a corticosteroid-sparing effect.
Book Publisher International (a part of SCIENCEDOMAIN International) · 2022 · 0 citations
Crohn’s Disease: A Curable Disease Held Hostage?
AbstractThe current focus of Crohn’s disease therapy has been long sclerosed. Biologics produce temporary remissions in 40% of cases. They have yet to induce permanent remissions. FDA’s reliance on clinical validation through comparative, placebo controlled, double-blinded studies has created an impediment to acceptance of divergent alternated therapies as being within the standard of care. In so doing, FDA has basically has surrendered the therapeutic dialogue of Crohn’s disease to those who can pay from such studies.
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.
