DeCure for Hyperinsulinemic hypoglycemia, familial, 4
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperinsulinemic hypoglycemia, familial, 4 — 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 moduleHyperinsulinemic hypoglycemia, familial, 4 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 hyperinsulinemic hypoglycemia, familial, 4 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
hydroxyacyl-CoA dehydrogenase (HADH) — HADH 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 caadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1F0Y · 1.8 Å · ligand ACETOACETYL-COENZYME A (CAA). Experimental structure, not a prediction.
What the evidence adds up to
A 1997 case report describes one infant with persistent hyperinsulinemic hypoglycaemia treated with diazoxide for 4.5 years. The drug maintained normoglycaemia without any side effects, including hypertrichosis. This is a single patient, not a trial.
A 2018 study reports the first homozygous ABCC8 mutation causing hyperinsulinemic hypoglycaemia at birth that later evolved into complete insulin-deficient, sulfonylurea-responsive diabetes mellitus. The authors note that homozygous ABCC8 mutations usually cause severe diffuse hyperinsulinemic hypoglycaemia that is diazoxide unresponsive and requires surgery. In the family carrying this identical mutation, the clinical spectrum ranged from asymptomatic, mild symptomatic hypoglycaemia, severe hypoglycaemia, and insulin-deficient diabetes. The paper emphasises that patients with neonatal hyperinsulinemic hypoglycaemia due to ABCC8 mutations, especially those managed medically, need long-term follow-up because of the risk of developing diabetes later in life.
A 2024 review lists 16 genes implicated in hyperinsulinemic hypoglycaemia: GLUD1, GCK, SLC16A1, HK1, CACNA1D, KCNJ11, ABCC8, FOXA2, HNF1A, HNF4A, HADH, PGM1, UCP2, KCNQ1, PMM2, EIF2S3. It states that mutations can be diffuse or focal, affecting many or all pancreatic beta cells respectively. The review summarises genetic variations, diagnosis, and treatment but provides no new patient data or outcomes.
What is missing: prospective trials comparing diazoxide against surgery or other agents in genetically stratified patients, long-term registries tracking glucose control and diabetes conversion rates by mutation type, and funding for such studies in a rare disease where sample sizes are necessarily small.
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 · 1997 · 4 citations
Long-Term Diazoxide Treatment in Persistent Hyperinsulincmic Hypoglycemia of Infancy: A Case Report
AbstractLong-term diazoxide and somatostatin analogue have been used in the treatment of persistent hyperinsulinemic hypoglycemia of infancy albeit with some side effects. We report a case with persistent hyperinsulinemic hypoglycemia who has been on diazoxide therapy for 4.5 years. Diazoxide treatment maintained normoglycemia without causing any side effects, including hypertrichosis.
Diabetes Metabolic Syndrome and Obesity · 2024 · 4 citations · open access
Genetic Variations in Hyperinsulinemic Hypoglycemia: Active versus Inactive Mutations
AbstractAbstract: Hyperinsulinemic Hypoglycemia (HH) is a rare condition that affects newborn children in the postnatal period, represented by dangerously low levels of blood glucose in a persistent manner, which puts the baby at high risk of multiple issues, especially regarding the brain cells if the baby does not take the appropriate medication or have the correct diagnosis. Hyperinsulinemic Hypoglycemia can happen due to an active or inactive mutation in 16 genes responsible for glucose metabolism and insulin secretion ( GLUD1 , GCK , SLC16A1 , HK1 , CACNA1D , KCNJ11 , ABCC8 , FOXA2 , HNF1A , HNF4A , HADH , PGM1 , UCP2 , KCNQ1 , PMM2 , EIF2S3 ). These mutations can take place in many forms, either defused or local, affecting several or all pancreatic beta cells respectively. This review summarizes genetic variations diagnosis and treatment of Hyperinsulinemic Hypoglycemia. Keywords: Hyperinsulinemic Hypoglycemia, nesidioblastosis, GLUD1 , hexokinase , FOXA2
Journal of Clinical Research in Pediatric Endocrinology · 2018 · 4 citations · open access
Congenital hyperinsulinism and evolution to sulfonylurea-responsive diabetes later in life due to a novel homozygous p.L171F ABCC8 mutation
AbstractHomozygous ABCC8 mutations cause severe persistent diffuse hyperinsulinemic hypoglycaemia (HH) which is usually diazoxide unresponsive and requires surgical therapy. In medically managed patients with congenital hyperinsulinism (CHI), disease symptoms become milder overtime. Hyperinsulinemic hypoglycemia at neonatal period and later diabetes have been reported in heterozygous mutation of HNF4A and HNF1A as well as heterozygous ABCC8 mutations What this study adds? We describe the first homozygous ABCC8 mutation with HH at neonatal period and evolution to complete insulin deficient, sulphonylurea responsive diabetes mellitus. Findings from present work which show a broad range of clinical spectrum from asymptomatic, mild symptomatic hypoglycemia, severe hypoglycemia as well as insulin deficient diabetes mellitus in family members with identical mutation confirms the phenotypical variations in ABCC8 mutations Present case report emphasizes the need for long-term follow up of patients with HH at neonatal period due to ABCC8 mutations, particularly those managed with medical therapy for risk of developing diabetes in later life.
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.
