DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperinsulinemic hypoglycemia — 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 moduleHyperinsulinemic hypoglycemia 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 hyperinsulinemic hypoglycemia 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 72-year-old woman with recurrent hypoglycaemia after a partial pancreatectomy for insulinoma had a plasma glucose of 42 mg/dl, insulin of 79.3 microU/ml, and HbA1c of 3.6%. After a 75 g oral glucose tolerance test her insulin reached 6623 microU/ml at 30 minutes while glucose was 88 mg/dl. Imaging failed to locate a tumour and she refused further surgery. A short-acting octreotide (50 microg) test improved glucose and insulin levels, and monthly injections of 20 mg long-acting octreotide controlled her hypoglycaemic symptoms for 10 months. The authors recommend a preliminary short-acting octreotide loading test before committing to long-acting treatment.
A 20-year-old male military paramedic with recurrent hypoglycaemia had factitious hypoglycaemia excluded and organic hyperinsulinaemic hypoglycaemia confirmed by prolonged fast. Endoscopic ultrasound and triple-phase CT were normal. Further history revealed hypoglycaemic episodes since childhood and a similar event in one brother. Because the patient was Ashkenazi Jewish, screening for two common founder mutations in the ABCC8 gene was performed. Direct sequencing showed homozygosity for the 3989-9 G>A mutation, confirming congenital hyperinsulinism of infancy. The authors note that rapid inexpensive screening for these founder mutations can avoid expensive, invasive and potentially dangerous diagnostic procedures.
One case report describes a child with persistent hyperinsulinaemic hypoglycaemia of infancy treated with diazoxide for 4.5 years. The drug maintained normoglycaemia without side effects, including no hypertrichosis. A 2024 review lists 16 genes in which mutations—active or inactive—can cause hyperinsulinaemic hypoglycaemia: GLUD1, GCK, SLC16A1, HK1, CACNA1D, KCNJ11, ABCC8, FOXA2, HNF1A, HNF4A, HADH, PGM1, UCP2, KCNQ1, PMM2, and EIF2S3. The review states that mutations can be diffuse or focal, affecting all or some pancreatic beta cells.
What is missing is a randomised trial comparing octreotide, diazoxide and other agents in adults with hyperinsulinaemic hypoglycaemia of undetermined cause, and a prospective study of genetic screening in adults presenting with this condition. The long-term safety data for octreotide in this indication remain limited to single case reports, and no trial has stratified patients by mutation type to guide drug selection.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Endocrine Journal · 2005 · 19 citations · open access
A Case of Hyperinsulinemia of Undetermined Origin, Successfully Treated with Long-acting Octreotide
AbstractMajor causes of fasting hypoglycemia in adults are insulinoma, factitious hypoglycemia and nesidioblastosis. The primary treatment for insulinoma is surgical removal of the tumor, but there are cases with hyperinsulinemia that cannot undergo surgery. Somatostatin analogue is one of the treatments used in such cases of insulinoma or persistent hyperinsulinemic hypoglycemia. We report here a patient who had undetermined hyperinsulinemia and was successfully treated with a long-acting somatostatin analogue, which had recently become available. The patient, a 72-year-old female, who had previously been diagnosed as insulinoma and undergone partial pancreatectomy, was admitted complaining of the recurrence of hypoglycemic attacks after an interval of ten years. On admission, hypoglycemia (42 mg/dl), hyperinsulinemia (IRI: 79.3 microU/m) and low HbA1c (3.6%) were present. In 75 g-OGTT at 30 min after load, IRI reached 6623 microU/ml, while plasma glucose level was 88 mg/dl. The anti-insulin antibody was not present. Since attempts at tumor localization by imaging techniques failed and the patient refused further examinations or surgical treatment, we recommended her to take a medication with a somatostatin analogue. Insulin suppression test using 50 microg of octreotide improved plasma glucose and IRI levels, suggesting the usefulness of the treatment, and a monthly administration of 20 mg of long-acting octreotide has successfully controlled her symptoms of hypoglycemia for 10 months. Our case demonstrated the utility of the long-acting somatostatin analogue for long-term treatment of undetermined hyperinsulinemia. A preliminary loading test using short-acting octreotide may be useful to determine appropriate medication, especially in cases who cannot receive surgical treatment.
The Journal of Clinical Endocrinology & Metabolism · 2016 · 18 citations · open access
Diagnosis of ABCC8 congenital hyperinsulinism of infancy in a 20 year-old man evaluated for factitious hypoglycemia.
AbstractCONTEXT: Hypoglycemia is a rare event in healthy adults, and the differential diagnosis includes many diseases, some of which are rare and easily missed. DESIGN, SETTING, DESCRIPTION: A 20-year-old male military paramedic was referred to our emergency department for investigation of recurrent hypoglycemia episodes during the previous months. Factitious hypoglycemia was excluded, and organic hyperinsulinemic hypoglycemia was diagnosed by the findings from a prolonged fast. The findings from endoscopic ultrasonography and triple-phase computed tomography were normal. Before additional diagnostic tests or exploratory surgery were performed, a deeper interrogation of the patient and his family revealed events compatible with episodes of hypoglycemia since childhood. Moreover, a single event of hypoglycemia during childhood was documented in 1 brother, suggesting the possibility of an inborn, inherited metabolic disease. Because the patient was Ashkenazi Jewish, we suspected the presence of 1 of 2 common founder mutations in the ABCC8 gene, which codes for 1 subunit of the β-cell adenosine triphosphate-sensitive potassium channel, known to cause congenital hyperinsulinism of infancy. Direct sequencing revealed homozygosity for the ABCC8 gene mutation 3989-9 G>A. CONCLUSIONS: The differential diagnosis of hyperinsulinemic hypoglycemia in a young healthy adult should include genetic disorders of glucose homeostasis. In the Ashkenazi population, rapid and inexpensive screening for 2 founder mutations can confirm the diagnosis, avoiding expensive, invasive, and potentially dangerous diagnostic procedures.
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
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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