DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for exocrine pancreatic insufficiency — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleExocrine pancreatic insufficiency maps to a 2-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 exocrine pancreatic insufficiency 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
CTR9 component of Paf1/RNA polymerase II complex (CTR9) — CTR9 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 9HVQ · 2.0 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 2005 randomised three-way crossover study of 24 chronic pancreatitis patients with maldigestion, 40,000 U lipase as enteric-coated mini-microspheres was taken just before meals, just after meals, or distributed along with meals. Before therapy, mean 13CO2 recovery was 23.8% (normal above 58.0%). During therapy, recovery was 53.9% when capsules were taken before meals, 60.6% when taken after meals, and 61.4% when taken along with meals. The proportion of patients who normalised fat digestion was 50% with before-meal dosing, 54% with after-meal dosing, and 63% with during-meal dosing. The authors concluded that efficacy may be optimised by administration during or after meals.
A 2012 study of 110 patients who had undergone pancreatic surgery (80 pancreatoduodenectomy, 30 distal pancreatectomy) used 13C-labelled mixed triglyceride breath tests to assess postoperative exocrine function. Acinar cell area in the pancreatic stump was significantly smaller after pancreatoduodenectomy than after distal pancreatectomy. Mean 7-hour cumulative 13C dose was significantly lower after pancreatoduodenectomy, and the rate of exocrine insufficiency was significantly higher. A significant but modest correlation was found between acinar cell area and breath test results (R = 0.35). The study did not test any drug.
A 2022 international survey of 252 pancreatologists found that 69% screen for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis, and only 21% repeat screening annually. 74% consider nutritional assessment standard. In cases of clinically evident steatorrhea, 71% prescribe enzyme supplementation. 40% refer more than half their patients to a dietician. 97% of respondents supported the need for more specific and tailored management instructions. The authors identified substantial practice variation and a lack of consensus despite existing guidelines.
A 2022 observational study of 17 patients with walled-off necrosis after necrotising pancreatitis evaluated pancreatic function at baseline, 3–6 months, and 12 months after discharge. At 12 months, Lundh’s test showed mild exocrine insufficiency in 29%, moderate in 7%, and severe in 50%. Fecal elastase was below 100 μg/g in 35% and below 200 μg/g in 59%. Only 24% required pancreatic enzyme substitution. Endocrine insufficiency developed in 24%, all of whom also had exocrine insufficiency. A 2018 Chinese consensus statement on exocrine insufficiency after pancreatic surgery was based on expert discussion rather than new trial data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Effect of the administration schedule on the therapeutic efficacy of oral pancreatic enzyme supplements in patients with exocrine pancreatic insufficiency: a randomized, three‐way crossover study
AbstractBACKGROUND: Oral pancreatic enzyme supplements should be properly administered in order to ensure an adequate gastric mixing with the food and simultaneous gastric emptying with the chyme. AIM: To evaluate, in a prospective, randomized, open, comparative, three-way, crossover study, the effect of the administration schedule on the efficacy of oral pancreatic enzymes for the treatment of exocrine pancreatic insufficiency. METHODS: Twenty-four consecutive chronic pancreatitis patients with maldigestion secondary to exocrine pancreatic insufficiency were treated with 40 000 U lipase in the form of capsules containing enteric-coated mini-microspheres. Capsules were taken just before meals (schedule A), just after meals (schedule B) or distributed along with meals (schedule C) for three consecutive 1-week crossover periods in a randomized order. Fat digestion before and during the three treatment periods was evaluated by an optimized mixed (13)C-triglyceride breath test. RESULTS: Before therapy, the (13)CO(2) recovery in the breath test was 23.8 +/- 15.8% (normal >58.0%). During therapy, the (13)CO(2) recovery tended to be higher when capsules were taken along with meals ((13)CO(2) recovery 61.4 +/- 21.4%) or just after meals ((13)CO(2) recovery 60.6 +/- 21.8%) than when taken just before meals ((13)CO(2) recovery 53.9 +/- 20.3%). The percentage of patients who normalized fat digestion under therapy was 50, 54 and 63% with schedules A, B and C respectively. CONCLUSIONS: The efficacy of pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency may be optimized by administration during or after meals.
Histological Loss of Pancreatic Exocrine Cells Correlates With Pancreatic Exocrine Function After Pancreatic Surgery
AbstractOBJECTIVE: The aim of this study was to investigate the relationship between histological findings of the pancreatic stump and postoperative pancreatic exocrine function. METHODS: One hundred ten patients including 80 patients undergoing pancreatoduodenectomy (PD) and 30 patients undergoing distal pancreatectomy (DP) were enrolled into this study. Postoperative exocrine pancreatic function was evaluated by 13C-labeled mixed triglyceride breath test. The areas of acinar cells, fibrotic tissues, and fatty replacement were histologically calculated in surgical specimens of the pancreatic stump. RESULTS: Histologically, acinar cell area of patients undergoing PD was significantly less than that of patients undergoing DP (P = 0.025). The values of the mean percentage dose 13C cumulative 7 hours of patients undergoing PD were significantly lower than those of patients undergoing DP (P < 0.001). The rate of pancreatic exocrine insufficiency in patients undergoing PD is significantly higher than that in patients with DP (P = 0.002). There was a significant correlation between acinar cell area of the pancreatic stump and the percentage dose 13C cumulative 7 hours (R = 0.35, P < 0.001). CONCLUSIONS: Pancreatoduodenectomy induced pancreatic exocrine insufficiency more frequently than DP. Histological loss of acinar cells in the pancreatic stump was strongly correlated with postoperative pancreatic exocrine function.
Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study
AbstractINTRODUCTION: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. METHODS: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. RESULTS: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. CONCLUSION: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.
Schweizer Archiv für Tierheilkunde · 2011 · 15 citations
Exokrine Pankreasinsuffizienz bei der Katze
AbstractWhile exocrine pancreatic insufficiency (EPI) is a well-documented functional disease of the pancreas in dogs, only a few reports characterize EPI in cats and no information is available on cats diagnosed with a function test from Europe. The present case series describes and discusses the clinicopathologic findings, diagnostics and therapy in 5 cats (18 months to 16 years) with EPI from Switzerland.
Somatostatin for the Prevention of Complications following Pancreatoduodenectomy
AbstractPancreatoduodenectomy (PD) may be followed by serious complications chiefly associated with exocrine pancreatic secretion. Somatostatin and its analogues are able to inhibit pancreatic secretion and thus have been advocated for the prevention of complications following pancreatic surgery. In four published multicentric randomized trials, octreotide administration was associated with a decrease in overall complication rate. However and surprisingly, the benefit is less clear when focusing on complications associated with pancreatic secretion as in pancreatic fistula or in high-risk patients (PD and nonfibrotic pancreas). The efficiency of other somatostatin analogues has not yet been assessed in randomized trials. In conclusion, further studies would be useful before routine prophylactic administration of somatostatin analogues can be recommended.
Scandinavian Journal of Gastroenterology · 2022 · 5 citations
Long-term changes of pancreatic function in patients with complicated walled-off necrosis
AbstractObjectives Walled-off necrosis (WON) is a serious complication to necrotizing acute pancreatitis with a high morbidity and mortality. The aim of this study was to investigate the long-term changes in pancreatic function, metabolic function and body composition in patients with WON.Material and methods Observational study including patients with WON who underwent endoscopic transmural drainage and necrosectomy. Patients were prospectively evaluated at baseline, 3–6 months after discharge, and 12 months after discharge. Patients were characterized with fecal elastase, blood samples, computer tomography, dual energy X-ray absorptiometry and Lundh’s test.Results The study includes 17 patients (11 men) with WON. The etiologies were gallstones (53%) alcohol intake (35%) and 12% had an unknown etiology. The body mass index (BMI) dropped during baseline and 3 months after discharge (p = .03) and increased 12 months after discharge (p = .002). Twelve months after discharge, 29% had mild exocrine insufficiency, 7% moderate insufficiency and 50% severe insufficiency based on the Lundh’s test. Fecal elastase was <100 μg/g in 35% and <200 μg/g in 59% 12 months after discharge. Only, 24% required pancreatic enzyme substitution. Endocrine insufficiency developed in 24%. These patients also had exocrine insufficiency.Conclusions A considerable proportion of patients with WON experience both endocrine and exocrine pancreatic insufficiency suggesting that long-term follow-up is needed in order to ensure adequate treatment.
[A consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency after pancreatic surgery (2018)].
AbstractBased on the latest references, combined with China's actual situation, a consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency after pancreatic surgery was developed by more than 20 Chinese extinguished experts, following 3 times of thorough discussions. This consensus discusses the definition, epidemiology, diagnosis, treatment and follow-up of pancreatic exocrine insufficiency after pancreatic surgery. The authors hope this consensus will promote the standard procedure of diagnosis and treatment of pancreatic exocrine insufficiency in China.
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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