DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperinsulinism — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHyperinsulinism maps to a 4-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 hyperinsulinism 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
ATP binding cassette subfamily C member 8 (ABCC8) — ABCC8 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6C3O · 3.9 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
A 2017 study examined a patient with transient congenital hyperinsulinism who carried heterozygous mutations in both ABCC8 (p.Tyr1293Asp) and KCNJ11 (p.Arg50Trp), inherited paternally. In an in vitro radioactive rubidium efflux assay, the activation of mutated KATP channels by diazoxide was reduced by 60.9% compared to wild-type channels. The authors state this may indicate a pathogenic effect on pancreatic beta-cell function leading to congenital hyperinsulinism, but they also note that conclusive evidence is still needed and that this proposed novel mechanism requires further investigation.
A 2006 case report describes a patient with congenital hyperinsulinism who was initially misdiagnosed with idiopathic cerebral convulsions and treated accordingly. The authors emphasise that diagnosis depends on strong clinical suspicion and thorough family history, and that normal random blood glucose or random insulin levels do not rule out the disease. Uncontrolled hypoglycaemia leads to seizures and long-term cerebral damage.
A 1989 publication states that recent advances in understanding the basis of congenital hyperinsulinism have led to new diagnostic and treatment strategies, and that applying these to general clinical practice should improve management and long-term outcomes. No specific drugs, response rates, or survival data are provided in that abstract. A 1940 abstract offers only a title and publication details, with no usable clinical data.
What remains missing is conclusive evidence for the proposed digenic mechanism, prospective trials testing whether combination mutation screening alters clinical management, and any data on whether the reduced diazoxide response observed in vitro translates to worse outcomes in patients. No drug other than diazoxide is mentioned in these abstracts, and no trial design or patient stratification strategy is described.
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 Pediatric Endocrinology and Metabolism · 2017 · 8 citations
Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?
AbstractBACKGROUND: Congenital hyperinsulinism (CHI) is frequently caused by mutations in one of the KATP channel subunits encoded by the genes ABCC8 and KCNJ11. The effect of simultaneous mutations in both of these genes on the pancreatic β-cell function is not known and patients with CHI carrying both ABCC8 and KCNJ11 mutations have not yet been reported. We questioned if a combination of heterozygous mutations in the ABCC8 and KCNJ11 genes could also lead to β-cell dysfunction presenting as CHI. METHODS: As a model, we used a patient with transient CHI that paternally inherited novel heterozygous mutations in ABCC8 (p.Tyr1293Asp) and KCNJ11 (p.Arg50Trp) genes. The pathogenic effects on the pancreatic β-cells function were examined in an in vitro functional study using radioactive rubidium efflux assay. RESULTS: We showed that the activation of the mutated KATP channels by diazoxide was decreased by 60.9% in the channels with the heterozygous combination of both mutations compared to the wild type channels. This could indicate the pathogenic effect on the pancreatic β-cell function leading to CHI although conclusive evidence is needed to be added. CONCLUSIONS: Our findings may widen the spectrum of genetic causes of CHI and suggest a novel pathogenic mechanism of CHI that must however, be further investigated.
American Journal of Clinical Pathology · 1940 · 1 citations
Annotations, Minor Contributions, Queries
AbstractAnnotations, Minor Contributions, Queries: A Simplified Test for Hyperinsulinism* Get access Emanuel M. Abrahamson Emanuel M. Abrahamson The Jewish and Greenpoint Hospitals, Brooklyn, N. Y. Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 10, Issue ts4_5, September 1940, Pages 138–139, https://doi.org/10.1093/ajcp/10.ts4_5.138 Published: 01 September 1940 Article history Received: 08 September 1939 Published: 01 September 1940
Dialnet (Universidad de la Rioja) · 1989 · 0 citations
La vida diaria en Talavera de la Reina desde la Restauración a la Segunda República: (1875-1936)
Abstractthe recent advances in the knowledge of the basis of congenital hyperinsulinism have resulted in new diagnostic and treatment strategies. Application of these aspects to general clinical practice will lead to an improvement of the management and long-term outcome of affected patients.
Pitfalls bei der Diagnose des kongenitalen Hyperinsulinismus: Ein Fallbericht und Übersicht der Literatur
AbstractBACKGROUND: Congenital hyperinsulinism is the most common cause for recurrent hypoglycaemia in neonates and infants. Uncontrolled hypoglycaemia leads to seizures and long-term cerebral damage. Often, the diagnosis is delayed because of nonspecific symptoms and confusing laboratory results. PATIENT: We report a patient with hyperinsulinism who was initially wrongly diagnosed as having idiopathic cerebral convulsions and treated accordingly. CONCLUSIONS: Diagnosis of congenital hyperinsulinism is based on a strong suspicion and a thorough family history. Normal random blood glucose or random insulin levels are not helpful in excluding this disease.
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.
