DeCure for Pancreatic hypoplasia-diabetes-congenital heart disease syndrome
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for pancreatic hypoplasia-diabetes-congenital heart disease syndrome — 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 modulePancreatic hypoplasia-diabetes-congenital heart disease syndrome 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 pancreatic hypoplasia-diabetes-congenital heart disease syndrome 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
acyl-CoA dehydrogenase very long chain (ACADVL) — ACADVL 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 faddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7S7G · 1.34 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
An Italian child with both pancreatic agenesis and an atrial septal defect was found to carry a novel GATA4 mutation (c1512C>T) that reduced protein activity. The mutation co-segregated with heart defects in the family but not with pancreatic agenesis. Screening of a panel of pancreas-development genes was negative, and the authors concluded the two conditions were independent events. No drug or intervention was tested.
A 1992 case report describes a patient with type I diabetes who died after pancreas transplantation; autopsy revealed hypoplasia of the native pancreas. The report offers no treatment data and no genetic analysis.
A 2013 case report describes a very low birth weight infant with pancreatic agenesis, congenital diaphragmatic hernia, and congenital heart disease (ventricular septal defect and patent ductus arteriosus). Failure to gain weight was improved by subcutaneous insulin, pancreatic enzyme administration, and a medium-chain-triglyceride-enriched formula. The infant was discharged from hospital. This is a single case, not a trial.
A 2021 case report identifies a novel homozygous PTF1A distal enhancer variant in an infant with neonatal diabetes and normal pancreatic imaging. The literature review noted that most patients with PTF1A variants had intrauterine growth restriction and imaging evidence of pancreatic agenesis or hypoplasia. No drug intervention was studied.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Diabetic Medicine · 2010 · 53 citations
Genetic investigation in an Italian child with an unusual association of atrial septal defect, attributable to a new familial <i>GATA4</i> gene mutation, and neonatal diabetes due to pancreatic agenesis
AbstractAIMS: Permanent neonatal diabetes is a rare condition affecting 1 in 300,000-400,000 live births; only in 60% of cases it is possible to identify the genetic defect. The condition of pancreatic agenesis is rarer still. Only two genes are known to determine this phenotype: PDX-1 and PTF1A. Congenital heart defects are among the most common developmental anomalies, affecting 1% of newborns, and the GATA4 gene is less frequently involved in these disorders. An Italian child with pancreatic agenesis and an atrial septal defect was genetically investigated to elucidate whether the association of the two pathologies was casual, or represented a new pancreatic/cardiac syndrome. METHODS: A panel of pancreas development genes, including GCK, Kir6.2, PTF1A, PDX-1, HNF-1A, NgN3, SOX17, SOX7, SOX9, INS, HNF1-B and SUR1 plus the GATA4 gene, were screened for characterization of pancreatic agenesis and cardiac defect. RESULTS: Screening for genes causing permanent neonatal diabetes was negative. A novel mutation in GATA4 (c1512C>T) was detected and functional characterization confirmed a reduced activity of the protein. In the family members, the GATA4 mutation co-segregates with a cardiac phenotype, but not with pancreatic agenesis. CONCLUSIONS: We describe the first report of pancretic agenesis with an associated cardiac defect and a mutation in the GATA4 gene. We could not establish that the GATA4 mutation was causative for pancreatic agenesis and further genetic investigation to detect the genetic cause of the pancreas agenesis was unsuccessful. We conclude that, the two pathologies are attributable to two independent events.
Hypoplasia of the Pancreas in a Patient with Type I Diabetes ellitus
AbstractPancreatic hypoplasia is an uncommon developmental defect that has not been well documented in association with type I diabetes mellitus. We report the case of a patient with an atypical clinical onset of type I diabetes mellitus who died following pancreas transplantation. Autopsy showed the surprising finding of hypoplasia of the native pancreas with other features indicating the concurrence of type I diabetes mellitus. These findings lead to speculation about the occurrence and interaction of these two diseases in our patient.
American Journal of Perinatology Reports · 2013 · 4 citations · open access
Pancreatic Agenesis with Congenital Diaphragmatic Hernia and Congenital Heart Disease: A Case Report
AbstractPancreatic agenesis is a rare disease that causes neonatal diabetes mellitus and exocrine pancreatic insufficiency. We report the case of a very low birth weight infant with congenital diaphragmatic hernia, and congenital heart disease (ventricular septal defect and patent ductus arteriosus). Failure to gain weight, despite well-managed respiratory and heart failure, was improved by infusion of subcutaneous insulin, administration of pancreatic enzyme, and nutrition of medium-chain-triglyceride -enriched formula. This is the first case of pancreatic agenesis with both malformations where the patient is discharged from the hospital. Early diagnosis and adequate treatments to compensate pancreatic function may prevent mortality and improve growth.
Iranian Journal of Pediatrics · 2021 · 2 citations · open access
Neonatal Diabetes Due to a Mutation in the Distal PTF1A Enhancer: A Case Report and Literature Review
Abstract: Biallelic variants in the pancreas-specific transcription factor 1A (PTF1A) gene are a rare cause of permanent neonatal diabetes. We report a case of neonatal diabetes with unique clinical manifestations. The clinical diagnosis of the affected infant was confirmed by insufficient endocrine and exocrine pancreas activity; however, the pancreas was normal in imaging. Molecular analyses identified a novel homozygous single nucleotide variant (Chr10, g.23508441T > G), affecting a highly conserved nucleotide within a distal enhancer of the PTF1A gene. The literature review showed that most of these patients had IUGR and imaging evidence of pancreatic agenesis or hypoplasia. We suggest that pancreatic imaging and evaluation of exocrine pancreas function can help early confirmation of the diagnosis in patients with permanent neonatal diabetes.
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.
