DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Diarrhea — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDiarrhea maps to a 31-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 diarrhea 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
regulator of G protein signaling 17 (RGS17) — RGS17 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6AM3 · 1.53 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
Diarrhoeal illnesses remain a major cause of morbidity and mortality worldwide, with most cases caused by bacteria, viruses, or parasites. A 2010 review of prolonged and persistent diarrhoea in children notes that these episodes, though less common than acute diarrhoea, contribute significantly to the global burden and are linked to malnutrition in a vicious cycle. The review states that increased use of WHO-recommended zinc therapy for all children with diarrhoea in developing countries would reduce morbidity and mortality, and that yogurt-based or amino-acid based diets may accelerate recovery in children with persistent diarrhoea. The same review calls for further research into recognition, prevention, and treatment of prolonged and persistent diarrhoea in resource-limited settings.
A 2010 open-label randomised trial compared the symbiotic formulation Flortec (containing Lactobacillus paracasei B-21060) with lactobacillus GG (FlorVis GG) in 174 adults with acute presumed infectious diarrhoea treated in primary care. The mean duration of diarrhoea from start of treatment was 4.24 days in the Flortec group versus 5.09 days in the FlorVis group, a difference that was not statistically significant (P=0.09). Clinical success rates for absence of abdominal pain and absence of diarrhoea were statistically superior in the Flortec group by Kaplan-Meier analysis (P=0.05 for both). The physician judged overall efficacy as good or very good in 91.8% of Flortec patients versus 83.7% of FlorVis patients (P=0.003). Both treatments had negligible and similar adverse event rates.
A 2006 retrospective chart review evaluated oral rifaximin in 19 patients with Clostridium difficile-associated diarrhoea, 14 with newly diagnosed disease and 5 with recurrent disease. Patients received rifaximin 400 mg twice or three times daily for 10 to 14 days. At the end of treatment, 17 patients (89%) had complete resolution of symptoms, with an average time to symptom relief of 6.7 days. Two patients (10%) experienced recurrence within 30 days post-treatment. The authors note that failure rates of 22% with metronidazole have been reported, and that appropriate treatment for recurrent CDAD is not well defined. They conclude that randomised placebo-controlled studies are warranted.
A 2010 review on defining causality in emerging agents of acute bacterial diarrhoeas notes that advances in molecular biology have revealed the complexity of the gut microbiome, and that potential agents of diarrhoea may also be found in healthy individuals. The review proposes that research should address appropriate matched controls and integrate findings from medical microbiology, epidemiology, and molecular biology. What remains missing for all these approaches are adequately powered randomised controlled trials, particularly in resource-limited settings, and better patient stratification to distinguish infectious from non-infectious causes and to identify those most likely to benefit from specific 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 Gastroenterology · 2010 · 39 citations
Update on prolonged and persistent diarrhea in children
AbstractPURPOSE OF REVIEW: To highlight recent advances in our understanding of prolonged episodes of acute diarrhea and persistent diarrhea in children. The focus is on the contribution of these illnesses to the global burden of diarrhea, their impact on childhood growth and development, novel epidemiologic links between prolonged and persistent diarrheal episodes, and strategies for their prevention and management. RECENT FINDINGS: Although less common than acute diarrhea, prolonged and persistent episodes of diarrhea in childhood constitute a significant portion of the global burden of diarrhea. These episodes also play a key role in the vicious cycle of childhood diarrhea and malnutrition in which undernutrition is both a risk factor and an outcome of diarrhea. Increased efforts to provide WHO-recommended zinc therapy for all children with diarrhea in developing countries will significantly reduce morbidity and mortality. In children who develop persistent diarrhea, yogurt-based or amino acid-based diets may accelerate their recovery. SUMMARY: In addition to increased implementation of strategies already known to effectively prevent and manage acute diarrhea, further research is needed to address the recognition, prevention, and treatment of prolonged episodes of acute diarrhea and persistent diarrhea in resource-limited settings.
Journal of Clinical Gastroenterology · 2010 · 19 citations
Clinical Trial on the Efficacy of a New Symbiotic Formulation, Flortec, in Patients With Acute Diarrhea
AbstractOBJECTIVES: Few randomized studies have been carried out on adult patients affected by acute diarrhea especially in primary care, which is the natural context for this kind of disorder. Lactobacillus paracasei B 21060 is a novel strain of lactobacillus, which has been shown to be effective in relieving symptoms associated with diarrhea of irritable bowel syndrome subtype and in shortening diarrhea duration. In this study, we compared the therapeutic efficacy, safety, and tolerability of a new symbiotic formulation, Flortec, containing L. paracasei B-21060, with lactobacillus GG (FlorVis GG) in the treatment of acute presumed infectious diarrhea. METHODS: Fourteen general practitioners working in the Perugia health authority district carried out a randomized controlled, parallel-group, open trial in 174 adult patients suffering from acute diarrhea (87 enrolled in the Flortec group and 87 in the FlorVis group). Both the products were administered according to their standard recommended dosage. The main efficacy criterion was the duration of diarrhea after beginning treatment. Treatment duration was 10 days. Enrolled patients kept a careful track of their symptoms noting them in a personal diary for 12 days. RESULTS: The 2 groups resulted to be homogeneous at baseline with regard to prognostic variables. The mean duration of diarrhea from the start of treatment in the Flortec group was 4.24 (2.73 SD) days versus 5.09 (3.72 SD) days in the FlorVis group (P=0.09).Clinical success rates in terms of absence of abdominal pain and absence of diarrhea (defined as <2 bowel movements of watery or loose stool consistency) recorded at different time-points were statistically superior in the Flortec group (Kaplan-Meyer P=0.05 for both the symptoms). The physician judged that overall efficacy was good or very good in 91.8% of the patients in the Flortec group. The corresponding value in the FlorVis group was 83.7% (P=0.003). The 2 treatments showed a very good tolerability profile, with negligible and similar adverse event rates and similar concomitant medication usage rates. CONCLUSIONS: Oral therapy with Flortec proved to be more effective than FlorVis GG in the treatment of acute diarrhea in adults treated at a primary care setting.
Defining Causality in Emerging Agents of Acute Bacterial Diarrheas: A Step Beyond the Koch’s Postulates
AbstractDiarrheal illnesses account for significant morbidity and mortality worldwide. Most cases of diarrhea are caused by bacteria, viruses or parasites. Advances in molecular biology and epidemiology have allowed the identification of emerging pathogens that may cause or, at least, may be associated with diarrhea. However, the same advances have also revealed the complexity of the gut microbiome, suggesting that a potential agent of diarrhea may also been found in healthy individuals. In addition, most of the newly identified emerging agents of diarrhea are ubiquitous and have not yet fulfilled Koch's postulates. Research investigations should address appropriate matched controls and integrate findings from medical microbiology, epidemiology and molecular biology. This integrative approach should provide insights to our knowledge regarding exposition to common source or risk factors. Here, we aim to review some of these emerging bacterial agents of diarrheas and propose guidelines or prescriptions that may help in defining causality.
Korean Journal of Gastroenterology · 2013 · 8 citations · open access
Efficacy of Fenoverine and Trimebutine in the Management of Irritable Bowel Syndrome: Multicenter Randomized Double-blind Non-inferiority Clinical Study
AbstractBACKGROUND/AIMS: Antispasmodic agents have been used in the management of irritable bowel syndrome. However, systematic reviews have come to different conclusions about the efficacy in irritable bowel syndrome. Fenoverine acts as a synchronizer of smooth muscle in modulating the intracellular influx of calcium. We compared fenoverine with trimebutine for the treatment of patients with IBS. METHODS: A multicenter, randomized, double-blind, non-inferiority clinical study was conducted to compared fenoverine with trimebutine. Subjects were randomized to receive either fenoverine (100 mg three times a day) or trimebutine (150 mg three times a day) for 8 weeks. A total of 197 patients were analyzed by the intention-to-treat approach. The primary endpoint was the proportion of patients who had 30% reduction in abdominal pain or discomfort measured by bowel symptom scale (BSS) score at week 8 compared to the baseline. The secondary endpoints were changes of abdominal bloating, diarrhea, constipation, overall and total scores of BSS, and overall satisfaction. RESULTS: At week 8, fenoverine was shown to be non-inferior to trimebutine (treatment difference, 1.76%; 90% CI, -10.30-13.82; p=0.81); 69.23% (54 of 78 patients) of patients taking fenoverine and 67.47% (56 of 83 patients) of patients taking trimebutine showed 30% reduction in abdominal pain or discomfort compared to the baseline. There results of the secondary endpoints were also comparable between the fenoverine group and the trimebutine group. CONCLUSIONS: Fenoverine is non-inferior to trimebutine for treating IBS in terms of both efficacy and tolerability.
The American Journal of Gastroenterology · 2006 · 2 citations
Oral Rifaximin in Treatment of Clostridium difficile-Associated Diarrhea
AbstractPurpose: The prevalence and severity of Clostridium difficile–associated diarrhea (CDAD) is increasing. Up to 25% of patients experience recurrence after standard first-line therapy, and appropriate treatment for CDAD recurrence is not well defined. Failure rates of 22% with metronidazole have been reported, a substantial increase from historical failure rates of 2% to 10%. Rifaximin is an oral, nonsystemic antibiotic with broad-spectrum activity. Preclinical data support a role for rifaximin in treatment of CDAD. This retrospective chart review evaluated the safety and efficacy of rifaximin in the treatment of CDAD. Methods: Consecutive patients aged ≥18 years diagnosed with CDAD (based on time to last unformed stool, stool score, and C difficile–positive toxin assay) between March 2005 and April 2006 were treated with rifaximin 400 mg twice daily (b.i.d.) or 3 times daily (t.i.d.) for 10 to 14 days. Response was assessed by resolution of clinical symptoms, CDAD recurrence 30 days posttreatment, and incidence of adverse events (AEs). Results: 19 patients (mean age, 60 y) with CDAD were identified; 14 (74%) with newly diagnosed disease and 5 (26%) with recurrent disease. Those with recurrent CDAD had previously received oral vancomycin (N = 4) or metronidazole (N = 1) as first-line therapy. All patients received rifaximin 400 mg b.i.d. (N = 1) or t.i.d. (N = 18), with a majority (89%) treated for 14 days. At the end of rifaximin treatment, 17 patients (89%) had complete resolution of symptoms, with an average time to symptom relief of 6.7 days. Only 2 (10%) of 19 patients treated with rifaximin experienced CDAD recurrence (days 12 and 15 posttreatment). Rifaximin was well tolerated with no discontinuations due to AEs. Overall, there were 3 reports each of headache and nausea. Conclusions: Rifaximin 800 mg/d or 1200 mg/d was well tolerated and effectively resolved clinical symptoms of CDAD. In addition, rifaximin prevented CDAD recurrence in a majority of patients. Randomized, placebo-controlled studies are warranted to further investigate the role of rifaximin in CDAD treatment and prevention.
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.
