DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for neonatal diabetes mellitus — screening already-approved drugs against its 11-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNeonatal diabetes mellitus maps to a 11-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 neonatal diabetes mellitus 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
insulin (INS) — INS 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.
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helix sheet hc4drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6TC2 · 1.36 Å · ligand 4'-HYDROXYCINNAMIC ACID (HC4). Experimental structure, not a prediction.
What the evidence adds up to
Neonatal diabetes mellitus is hyperglycaemia within the first month of life requiring insulin. It may be transient or permanent. Management is complicated by low subcutaneous fat and the need for tiny insulin doses. Two case reports describe successful use of continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM) in infants with transient neonatal diabetes; one patient achieved normoglycaemia and stopped treatment at 2 months of age. A 2005 paper presents three cases, two treated with CSII and one with conventional insulin, and offers suggested treatment guidelines for this approach.
Genetic testing is critical. Activating mutations in the ATP-sensitive potassium channel subunits ABCC8 and KCNJ11 cause about half of permanent neonatal diabetes and some transient cases. A 2021 Italian retrospective analysis of 22 patients with KATP-related transient neonatal diabetes (TNDM) and 12 patients with 6q24-related TNDM found distinct features: 6q24 patients had earlier median onset (1 week vs 4 weeks) and lower birth weight (−2.27 SD vs −1.04 SD), while KATP patients had longer median time to remission (21.5 weeks vs 12 weeks). Two KATP patients entered remission without any drug therapy. One proband with an ABCC8 variant previously linked to permanent diabetes entered a 7-year remission after one year of sulfonylurea. Seven KATP patients were successfully managed on sulfonylurea monotherapy; four relapsing 6q24 patients were treated with insulin, metformin, or combination therapy. A 2010 review notes that identifying KATP mutations allows patients to switch from insulin to sulfonylureas, and that neurological dysfunction may improve in some cases.
A 2018 review states that treatment depends on the mutation type, with patients responding to either insulin or sulfonylurea. A 2024 case report of an infant with TNDM of unknown cause (genetic testing excluded most known mutations) was treated with CSII and CGM until remission at 2 months, and the authors call CSII and CGM safe and effective. The 2010 review emphasises that other causes include proinsulin mutations, FOXP3 mutations, homozygous glucokinase mutations, and Wolcott-Rallinson/EIF2AK3 diabetes, and that much remains unknown about optimising therapy with available agents.
What is still missing: prospective trials comparing CSII versus sulfonylurea in genetically stratified infants, long-term follow-up data on neurodevelopmental outcomes after early sulfonylurea treatment, and cost-effectiveness studies of routine genetic testing in all neonatal diabetes cases. Without these, treatment decisions remain based on small case series and retrospective data.
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 Paediatrics and Child Health · 2005 · 46 citations
Neonatal diabetes mellitus: Insulin pump as an alternative management strategy
AbstractNeonatal diabetes mellitus (hyperglycaemia within the first month of life, with an insulin requirement) may be transient or permanent. Management is complex, due to lack of subcutaneous fat and the need for small doses of insulin, and may be complicated by additional medical problems. Three cases are presented, the first of which was treated with conventional insulin therapy. The latter two were successfully treated with subcutaneous insulin pump therapy. We present suggested guidelines for treatment of neonatal diabetes, using this novel approach to management.
Current Opinion in Endocrinology Diabetes and Obesity · 2010 · 43 citations
Update in neonatal diabetes
AbstractPURPOSE OF REVIEW: Here we give context to new data on neonatal diabetes mellitus, a rare group of insulin-requiring monogenic forms of diabetes presenting at birth or shortly thereafter. Genetic studies are critical in the diagnosis and treatment of these patients. The most common causes of neonatal diabetes are activating mutations in the two protein subunits of the ATP-sensitive potassium channel. These are responsible for about half of all cases of permanent neonatal diabetes and some cases of transient neonatal diabetes. Identification of these mutations allows patients treated with insulin to be transferred to sulfonylureas, but associated conditions and other causes must be considered. RECENT FINDINGS: Recent data suggest that neonatal diabetes is more common than previously thought, with variable presentations. Continued studies provide further evidence for amelioration of developmental and neurological dysfunction exhibited by a significant proportion of patients. Abnormalities of chromosome 6q24 remain the most common cause of transient neonatal diabetes. Other causes of neonatal diabetes being studied include mutations in proinsulin, FOXP3 mutations in immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, homozygous glucokinase mutations, and Wolcott-Rallinson/EIF2AK3 diabetes. SUMMARY: We still have much to learn about the different forms of neonatal diabetes, their associated clinical features, and the optimization of therapy using a growing number of available therapeutic agents.
Journal of Pediatric Endocrinology and Metabolism · 2005 · 26 citations
Neonatal Diabetes Mellitus: Patient Reports and Review of Current Knowledge and Clinical Practice
AbstractNeonatal diabetes mellitus (NDM) is a rare disease reported to have an incidence of one in 400,000 to 500,000 live births. The disorder may be more common as it is not routinely considered a diagnostic possibility by many neonatologists who may routinely use insulin to treat neonatal hyperglycemia. NDM can be grouped into two distinct clinical entities--transient and permanent--based on certain features detailed herein; however, distinction between the two categories can only be definitely made in hindsight. Treatment is with insulin; however, determining the correct dose and method of delivery is often challenging, given the sensitivity of neonates to insulin and the risk of hypoglycemia. We report the successful use of Glargine insulin in the treatment of three infants with NDM, review the recent discoveries, and discuss guidelines for the care of newborns with NDM.
Mitiglinide: A Novel Agent for the Treatment of Type 2 Diabetes Mellitus
AbstractOBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of mitiglinide, a rapid-acting insulin secretion-stimulating agent to determine its potential role in therapy for the treatment of type 2 diabetes mellitus. DATA SOURCES: A MEDLINE search (1966-May 2010) was conducted for English-language, human studies using the terms mitiglinide, KAD 1229, S 21403, and meglitinide analogs. Abstracts presented at the American Association and European Association for the Study of Diabetes annual meetings from 2005 to 2009 were also evaluated for relevant data. STUDY SELECTION AND DATA EXTRACTION: Articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of mitiglinide were reviewed. DATA SYNTHESIS: Mitiglinide has been shown through small clinical studies (N <400) to modestly decrease hemoglobin A(1c), postprandial hyperglycemia, and oxidative stress and inflammatory markers associated with postprandial hyperglycemia. Mitiglinide exerts its hypoglycemic activity by closing adenosine triphosphate (ATP)-sensitive potassium channels in the β-islet cells of the pancreas. This agent has a rapid onset and short duration of action, mimicking a physiologic pattern of insulin release in nondiabetic people. Studies suggest a starting dose of 5 mg 3 times daily with meals and a maximum dose of 20 mg 3 times daily. Overall, mitiglinide is well tolerated, with the most common adverse effect being hypoglycemia. CONCLUSIONS: Mitiglinide is the third agent in the class of meglitinides that targets postprandial hyperglycemia. Because of a more intensive dosing regimen, potential cost, and lack of studies assessing the clinical impact of mitiglinide therapy on oxidative stress and inflammatory markers secondary to postprandial hyperglycemia, we cannot recommend this therapy over currently approved therapies.
SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital · 2018 · 3 citations · open access
Neonatal diabetes mellitus
AbstractNeonatal diabetes is a rare cause of hyperglycemia in the neonatal period. It is caused by mutations in genes that encode proteins playing critical roles in normal functions of pancreatic beta cells. Neonatal diabetes is divided into temporary and permanent subtypes. Treatment is based on the correction of fluid-electrolyte disturbances and hyperglycemia. Patients respond to insulin or sulfonylurea treatment according to the mutation type. Close glucose monitoring and education of caregivers about diabetes are vital.
Transient Neonatal Diabetes Mellitus with an Unknown Cause in a 1-Month-Old Infant: A Case Report
AbstractTransient neonatal diabetes mellitus (TNDM) is a genetically heterogeneous form of neonatal diabetes characterized by hyperglycemia that remits during infancy with a tendency to recur in later life. This case report presents the history of a male infant with transient neonatal diabetes mellitus. The patient was treated with a continuous subcutaneous insulin infusion (CSII) and a continuous glucose monitoring (CGM) system until the age of 2 months, when the normoglycemia connected with a withdrawal of treatment was noted. The genetic test results excluded the majority of known mutations related to TNDM. This case report focuses on various genetic mutations and the clinical features connected with them that cause TNDM and highlights the difficulties in the diagnostic and therapeutic processes of this disease. CSII and CGM systems seem to be a safe and effective treatment option in TNDM and may be used in the therapy.
Yearbook of pediatric endocrinology · 2021 · 1 citations
Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy.
AbstractObjective: Transient neonatal diabetes mellitus (TNDM) is caused by activa ting mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We want ed to assess whether these different genetic aetiologies result in distinct clinical features. Design: Retrospective analysis of the Italian data set of patients wit h TNDM. Methods: Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results: Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose value s, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in K ATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal di abetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with K ATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated w ith insulin, metformin or combination therapy. Conclusions: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients w ith macroglossia and/or umbilical hernia. Remission of diabetes without pharmaco logical therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remis sion of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.
The Journal of Ad-din Women s Medical College · 2024 · 0 citations · open access
Transient neonatal diabetes in a very small sick newborn: A case Report
AbstractHyperglycemia in neonatal period is a common metabolic disorder, especially seen in preterm low birth weight and critically ill newborns. The estimated incidence of this condition is around 45%–80%. But Neonatal diabetes mellitus (NDM)is a rare neonatal disease, which has an incidence of approximately 1 in 90,000–160,000 neonates worldwide. Herein we report an extreme preterm, extreme low birth weight, male neonate with transient neonatal diabetes mellitus who was treated with intravenous insulin initially and then subcutaneous insulin Glargine. An adequate glycemia was achieved at 3 weeks of life. The Journal of Ad-din Women's Medical College; Vol. 12 (1), Jan 2024; p 44-46
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.
