DeCure for Neonatal diabetes mellitus with congenital hypothyroidism
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for neonatal diabetes mellitus with congenital hypothyroidism — 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 moduleNeonatal diabetes mellitus with congenital hypothyroidism 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 neonatal diabetes mellitus with congenital hypothyroidism 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
interleukin 2 receptor subunit alpha (IL2RA) — IL2RA 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9KMC · 2.97 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a rat model, neonatal hypothyroidism induced by giving lactating mothers 6-propyl-2-thiouracil led to lasting changes in the adult male offspring. During an intravenous glucose tolerance test, the plasma glucose of the hypothyroid group (13.18 ± 0.59 mmol/l) was significantly higher at 5 minutes than controls (11.54 ± 0.47 mmol/l), but plasma insulin concentrations and glucose-stimulated insulin secretion were not significantly different. The homeostasis model assessment of insulin resistance was higher in the hypothyroid group (9.1 ± 1.0) versus controls (4.5 ± 0.6), and the area and diameter of pancreatic islets were significantly smaller. The authors concluded that neonatal hypothyroidism can alter carbohydrate metabolism in euthyroid adult offspring, possibly increasing susceptibility to glucose intolerance and type 2 diabetes later in life.
Congenital hypothyroidism (CH) is one of the most common preventable forms of mental retardation. Primary CH can be due to abnormal thyroid gland formation (dysgenesis, about 85% of cases) or defective thyroid hormone synthesis by a structurally normal gland (dyshormonogenesis). Genetic defects are found in a very low proportion of dysgenesis cases, whereas dyshormonogenesis is usually genetic with autosomal recessive inheritance. A 2018 review lists all known monogenetic causes of primary CH and promising new candidate genes.
A case report of a 3-year-old boy diagnosed with CH as a newborn, who was left untreated, experienced significant growth failure and developmental delay, emphasising the importance of consistent adherence to L-thyroxine treatment in infancy and early childhood. Another case report describes a male infant with congenital hypoparathyroidism who developed primary hypothyroidism at 3 months and insulin-dependent diabetes mellitus at 25 months, along with widespread neurologic dysfunction, renal hypoplasia, and other abnormalities; he died of multiorgan failure at 29 months, and no molecular mechanism was identified.
No abstract in this set reports a drug repurposed for neonatal diabetes mellitus with congenital hypothyroidism. What is missing is any clinical trial or case series testing a specific drug for this combined condition, as well as patient stratification by the underlying genetic defect and funding for such research.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PubMed · 2013 · 18 citations
Effect of neonatal hypothyroidism on carbohydrate metabolism, insulin secretion, and pancreatic islets morphology of adult male offspring in rats.
AbstractBACKGROUND: Neonatal hypothyroidism has serious effects on growth, development, and metabolism. AIM: This study aims to investigate the effects of the neonatal hypothyroidism on carbohydrate metabolism, islet insulin secretion and morphology of the pancreatic islets in adult male offspring. MATERIALS/SUBJECTS AND METHODS: Lactating mothers of Wistar rats consumed 0.02% solution of 6-propyl-2-thiouracil during the weaning period (neonatal hypothyroid group), while mothers of the control group drank merely tap water. Body weight and survival of pups were followed up. Intravenous glucose tolerance test was performed in adult male offspring and 5-6 weeks later, glucose-stimulated insulin secretion (GSIS) was evaluated. RESULTS: During the glucose tolerance test, plasma glucose level of the neonatal hypothyroid group (13.18 ± 0.59 mmol/l) was significantly higher at 5 min compared to the control group (11.54 ± 0.47 mmol/l), whereas plasma insulin concentrations and GSIS of the groups was not significantly different. Homeostasis model assessment of insulin resistance of adult male offspring of the hypothyroid group (9.1 ± 1.0) was significantly higher as compared to the control group (4.5 ± 0.6). Area (14,613.0 ± 2646.3 μm2) and the diameter of the islets (147 ± 3.0 μm) of the neonatal hypothyroid group were significantly lower, as compared to the control group (32,886.3 ± 4690.3 and 206.6 ± 5.9 μm2 and μm, respectively). CONCLUSION: Neonatal hypothyroidism can alter carbohydrate metabolism in euthyroid adult offspring, which may increase susceptibility to the development of glucose intolerance and occurrence of Type 2 diabetes later in life.
AbstractCongenital hypothyroidism (CH) is one of the most common preventable forms of mental retardation and since the implementation of neonatal screening programs in the mid-1970s, early detection and treatment have proven to be very successful in preventing brain damage. CH may be of thyroidal (= primary) or of hypothalamic-pituitary (= central) origin. Primary CH may be due to abnormal thyroid gland formation (dysgenesis) or defective thyroid hormone syntheses by a structurally normal gland (dyshormonogenesis). While thyroid dysgenesis is the most common form of CH, accounting for approximately 85% of cases, genetic defects are only found in a very low proportion of patients. On the other hand, thyroid dyshormonogenesis is less common, but is usually a genetic condition with autosomal recessive inheritance. In this review we provide an overview of all known monogenetic causes of primary CH, including promising new candidate genes. In addition, alternative genetic mechanisms are discussed.
Case Reports in Endocrinology · 2012 · 3 citations · open access
Effect of Prolonged Discontinuation of L-Thyroxine Replacement in a Child with Congenital Hypothyroidism
AbstractWhen diagnosed through neonatal screening and treated promptly and adequately, infants with congenital hypothyroidism (CH) experience normal physical growth and neurological development. Here we present a 3-year-old boy diagnosed with CH as a newborn, who was subsequently left untreated and experienced significant growth failure and developmental delay. This case emphasizes the importance of a consistent adherence to treatment in preventing such complications, especially in infancy and early childhood.
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.
