DeCure for Diabetes mellitus, transient neonatal, 3
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for diabetes mellitus, transient neonatal, 3 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDiabetes mellitus, transient neonatal, 3 maps to a 1-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 diabetes mellitus, transient neonatal, 3 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
glucokinase (GCK) — GCK 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 2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4DCH · 1.79 Å · ligand (2R)-3-cyclopentyl-2-[4-(methylsulfonyl)phenyl]-N-(1,3-thiazol-2-yl)propanamide (4DC). Experimental structure, not a prediction.
What the evidence adds up to
Transient neonatal diabetes mellitus is a rare genetic disease, occurring in roughly 1 in 90,000 live births, defined by severe hyperglycaemia before age one that requires either transient or permanent insulin treatment. The most frequent genetic causes are abnormalities of the 6q24 locus and mutations of the ABCC8 or KCNJ11 genes, which code for the pancreatic beta-cell potassium channel. Patients with a 6q24 abnormality have lower birth weight and height, are younger at diagnosis and remission, and have a higher malformation frequency than those with ABCC8 or KCNJ11 mutations. Patients with ABCC8 or KCNJ11 mutations have neurological and neuropsychological disorders in all those tested carefully. Up to 86% of patients who achieve remission have recurrent diabetes when they reach puberty, regardless of the genetic origin.
90% of patients with an ABCC8 or KCNJ11 mutation, as well as those with 6q24 anomalies, can be successfully switched from insulin injections to oral sulfonylureas. Sulfonylureas improve insulin secretion in most patients with transient neonatal diabetes mellitus and provide effective glycaemic control. The disease is divided into transient, permanent, and syndromic categories based on the underlying genetic mutation. Some proposed non-genetic aetiologies include stress-related increases in counter-regulatory hormones, sepsis, and improper parenteral administration of glucose, steroids, or beta-adrenergic agents.
The evidence is limited to small case series and reviews; no large randomised controlled trials exist for this population. What is still missing is a prospective trial that stratifies patients by the specific genetic subtype (6q24 versus potassium channel mutations) and tracks long-term outcomes beyond puberty, including the rate and severity of neurological complications. Funding for such a trial is absent, and the rarity of the condition makes recruitment difficult without international collaboration.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Pediatrics · 2020 · 89 citations · open access
Neonatal Diabetes Mellitus
AbstractNeonatal Diabetes (ND) mellitus is a rare genetic disease (1 in 90,000 live births). It is defined by the presence of severe hyperglycaemia associated with insufficient or no circulating insulin, occurring before the age of one year. Such hyperglycaemia requires either transient treatment with insulin in about half of cases, or permanent insulin treatment. The disease is explained by two major groups of mechanism: malformation of the pancreas with altered insulin-secreting cells development/survival or abnormal function of the existing pancreatic β cell. The most frequent genetic causes of neonatal diabetes mellitus with abnormal β cell function are abnormalities of the 6q24 locus and mutations of the ABCC8 or KCNJ11 genes coding for the potassium channel in the pancreatic β cell. Other genes are associated with pancreas malformation or destruction of β cells. Clinically, compared to patients with an ABCC8 or KCNJ11 mutation, patients with a 6q24 abnormality have lower birth weight and height, are younger at diagnosis and remission, and have a higher malformation frequency. Patients with an ABCC8 or KCNJ11 mutation have neurological and neuropsychological disorders in all those tested carefully. Up to 86% of patients having remission have recurrent diabetes when they reach puberty, with no difference due to the genetic origin. All these results reinforce the importance of prolonged follow-up by a multidisciplinary paediatric team, and later doctors specialising in adult medicine. 90% of the patients with an ABCC8 or KCNJ11 mutation as well as those with 6q24 anomalies are amenable to a successful switch from insulin injection to oral sulfonylureas.
Journal of Healthcare Sciences · 2021 · 1 citations · open access
Epidemiology and Clinical Phenotypes and Presentations of Neonatal Diabetes
AbstractNeonatal diabetes mellitus is a rare condition that develops within the first months of life, usually as a result of a genetic abnormality. The condition has been defined as the presence of a severe form of hyperglycemia that requires adequate management and usually affected neonates and young infants. The disease has also been divided into two or three categories, upon which the clinical presentations of the affected patients usually depend. In the present study, we have reviewed the current literature to discuss the epidemiology, clinical phenotypes and presentations of patients suffering from neonatal diabetes. The condition is a rare one and some of the proposed etiologies may include a stress-related increase in the levels of counter-regulatory hormones, sepsis, and the increased or improper parenteral administration of -adrenergic agents, steroids, or glucose. Three main categories have been identified for neonatal diabetes, including transient, permanent, and syndromic diabetes, which vary based on the underlying genetic mutations. Various developmental and neurological disorders have been linked with the disease. Therefore, planning adequate interventions as early as possible is critical to enhancing the outcomes as some affected children are prone to depend on insulin therapy throughout their entire life.
Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) · 2019 · 1 citations · open access
Neonatal Diabetes Insipidus in a Palestinian Newborn
AbstractDiabetes insipidus is rare in newborn. There are two types of this disease: central and nephrogenic diabetes insipidus. A Palestinian infant was born at Shifa Women`s Hospital at full term by urgent cesarean section. At the age of 13 days he had fever, hypernatremia, polyuria, weight loss and low specific gravity of urine. The baby was diagnosed to have diabetes insipidus. The baby was successfully treated by fluid loss recovery by bottle feeding and intravenous 5% dextrose and sodium chloride solution. At home, they continued to correct fluid loss by bottle- feeding and drinking water.
Approach to the patients with transient neonatal diabetes mellitus
AbstractTransient neonatal diabetes mellitus is a kind of rare special types of diabetes. It should be distinguished from type 1 diabetes. Genetic analysis can be used to define the subtype of neonatal diabetes mellitus, which helps us to select the most appropriate treatment and to predict the disease recurrence. Sulfonylureas is able to improve insulin secretion in most patients with transient neonatal diabetes mellitus and provide effective glycemic control. A case of transient neonatal diabetes mellitus is reported in order to call attention to the diagnosis and treatment of this disease. (Chin J Endocrinol Metab, 2016, 32: 510-513)
Key words:
Transient neonatal diabetes mellitus; Gene; Sulfonylureas
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.
