DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for pancreatic agenesis 1 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePancreatic agenesis 1 maps to a 1-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 pancreatic agenesis 1 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.
What the evidence adds up to
In mice, deleting both Gata4 and Gata6 specifically in the pancreas caused severe pancreatic agenesis, disrupting progenitor cell proliferation, branching morphogenesis, and the differentiation of cells expressing CPA1 and NEUROG3. Deleting either gene alone produced only mild pancreatic defects that resolved after birth. These mouse studies were prompted by the finding that mutations in GATA6 are the most common known cause of human pancreatic agenesis, with GATA4 mutations implicated in only a single case. Before these GATA factors were identified, mutations in PDX1 and PTF1A had been reported in only five families with pancreatic agenesis.
Dorsal pancreatic agenesis is a separate, rarer malformation. A systematic review covering 2008 to 2015 found 53 new patients (7 children, 46 adults), bringing the total reported since 1911 to over 100 cases. Patients may be asymptomatic or present with abdominal pain, hyperglycaemia, diabetes mellitus, or pancreatitis. The review noted an association with non-alcoholic pancreatitis and neoplasia of the residual pancreas, advising an expectant clinical attitude. A 2024 case report describes a 74-year-old man with diabetes mellitus who had weight loss and loss of appetite; the report states that appropriate medical interventions can improve quality of life but does not specify which interventions.
Complete pancreatic agenesis and ventral pancreatic agenesis are incompatible with life. No drug treatment for any form of pancreatic agenesis is mentioned in any of these abstracts. What remains missing is any clinical trial of a pharmacological intervention, any evidence that a drug can restore pancreatic tissue or function in humans with these conditions, and any stratification of patients by the specific genetic mutation causing their agenesis.
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 Investigation · 2012 · 167 citations · open access
Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis
AbstractPancreatic agenesis is a human disorder caused by defects in pancreas development. To date, only a few genes have been linked to pancreatic agenesis in humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas-specific transcription factor 1a (PTF1A) reported in only 5 families with described cases. Recently, mutations in GATA6 have been identified in a large percentage of human cases, and a GATA4 mutant allele has been implicated in a single case. In the mouse, Gata4 and Gata6 are expressed in several endoderm-derived tissues, including the pancreas. To analyze the functions of GATA4 and/or GATA6 during mouse pancreatic development, we generated pancreas-specific deletions of Gata4 and Gata6. Surprisingly, loss of either Gata4 or Gata6 in the pancreas resulted in only mild pancreatic defects, which resolved postnatally. However, simultaneous deletion of both Gata4 and Gata6 in the pancreas caused severe pancreatic agenesis due to disruption of pancreatic progenitor cell proliferation, defects in branching morphogenesis, and a subsequent failure to induce the differentiation of progenitor cells expressing carboxypeptidase A1 (CPA1) and neurogenin 3 (NEUROG3). These studies address the conserved and nonconserved mechanisms underlying GATA4 and GATA6 function during pancreas development and provide a new mouse model to characterize the underlying developmental defects associated with pancreatic agenesis.
Neuroendocrinology · 2022 · 42 citations · open access
Streptozotocin, 1982–2022: Forty Years from the FDA’s Approval to Treat Pancreatic Neuroendocrine Tumors
AbstractIn May 1982, the US Food and Drug Administration (FDA) approved the use of streptozotocin to treat pancreatic neuroendocrine tumors (panNETs). Thus, this year marks 40 years since that landmark date. This review of streptozotocin to treat panNETs is intended to commemorate this anniversary. A historical perspective of the chemical structure, pharmacokinetics, and mechanism of action of streptozotocin is followed by data from prospective and retrospective clinical studies. The last section of the review addresses the latest aspects and takes note of the prospects that lie ahead on the future horizon of the use of streptozotocin to treat panNETs, including ongoing clinical trials.
Revista Española de Enfermedades Digestivas · 2016 · 33 citations · open access
Agenesis of the dorsal pancreas: systematic review of a clinical challenge
AbstractBACKGROUND: Agenesis of the dorsal pancreas is a rare malformation. Since 1911 and until 2008, 53 cases have been reported. Several authors have recently described the association of this anomaly with neoplasia of the ventral pancreas, thus we performed a systematic review of the literature from 2008 to 2015. METHODS: A systematic review of the MedLine and ISI Web of Science Databases from 2008 until 2015 was carried out, and 30 articles which met the inclusion criteria were identified that included a total of 53 patients: 7 children and 46 adults. CONCLUSIONS: Although dorsal pancreatic agenesis is a rare malformation, given its association with non-alcoholic pancreatitis and neoplasia of the residual pancreas, physicians should maintain an expectant attitude.
Journal of Clinical Investigation · 2012 · 26 citations · open access
GATA believe it: new essential regulators of pancreas development
AbstractUnderstanding the transcriptional mechanisms that underlie pancreas formation is central to the efforts to develop novel regenerative therapies for type 1 diabetes. Recently, mutations in the transcription factor GATA6 were unexpectedly shown to be the most common cause of human pancreas agenesis. In this issue of the JCI, Carrasco et al. and Xuan et al. investigate the role of Gata6 and its paralogue Gata4 in mouse embryonic pancreas and show that GATA factors are essential regulators of the proliferation, morphogenesis, and differentiation of multipotent pancreatic progenitors.
Indian journal of radiology and imaging - new series/Indian journal of radiology and imaging/Indian Journal of Radiology & Imaging · 2014 · 16 citations · open access
MR in complete dorsal pancreatic agenesis: Case report and review of literature
AbstractThe morphogenesis of the pancreas is a complex process having a very low frequency of anatomic variation. The congenital anomalies are rare. Complete pancreatic and ventral pancreatic agenesis are incompatible with life. Dorsal pancreatic agenesis is exceedingly rare with less than 100 cases reported in the world literature. Patients with this anomaly may be asymptomatic or may present with abdominal pain, hyperglycemia, diabetes mellitus, and acute or chronic pancreatitis. Such anomalies are rarely reported; therefore, clinical awareness of agenesis of the dorsal pancreas as a cause of these symptoms can expand the differential diagnosis and improve patient management.
Journal of Radiology Case Reports · 2024 · 0 citations · open access
Dorsal pancreas agenesis – A case report and review of literature
AbstractDorsal pancreas agenesis is a rare congenital anomaly that presents unique challenges in the realm of digestive and endocrine function.While the condition is uncommon, understanding its impact on pancreatic function and implementing appropriate medical interventions can significantly improve the quality of life for affected individuals.This is a case of a 74-year-old male patient with diabetes mellitus who presented with a history of loss of weight and loss of appetite.
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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