DeCure for Hypothyroidism, congenital, nongoitrous, 5
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for hypothyroidism, congenital, nongoitrous, 5 — 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 moduleHypothyroidism, congenital, nongoitrous, 5 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 hypothyroidism, congenital, nongoitrous, 5 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
NK2 homeobox 5 (NKX2-5) — NKX2-5 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 6WC2 · 2.1 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1949 study of patients treated for congenital hypothyroidism over thirteen to twenty-three years reported that physical development usually improved with treatment, but mental attainment frequently remained poor. The authors cited earlier longitudinal work on 23 children that supported this view. No survival or response rates were given.
Neonatal screening programmes introduced in the mid-1970s have allowed early detection and treatment, which a 2018 review states has proven very successful in preventing brain damage. Primary congenital hypothyroidism is either due to thyroid dysgenesis (abnormal gland formation, about 85% of cases) or dyshormonogenesis (defective hormone synthesis). Genetic defects are found in a very low proportion of dysgenesis cases, whereas dyshormonogenesis is usually genetic with autosomal recessive inheritance.
A 2012 study in Uberaba, Brazil, covering 88% of live-born children from 2001 to 2010, diagnosed 16 children with congenital hypothyroidism, an incidence of 1:2,017 screened. Etiological evaluation of 15 children found seven cases of thyroid dysgenesis, seven of dyshormonogenesis, and one transient hypothyroidism. The authors noted that both the incidence of congenital hypothyroidism and the proportion of dyshormonogenesis appeared increased in that region, but called for molecular studies to define the causes.
A 2020 in silico study examined five genes (NIS, PAX8, DUOX2, FOXE1, NKX2-1) involved in thyroid development and found consensus sequence motifs shared across these genes. The study did not test any treatment or patient outcomes. What remains missing is prospective trial data linking specific genetic findings to treatment response, larger population-based molecular studies to clarify regional incidence differences, and any evidence that current treatment regimens improve long-term cognitive outcomes beyond the early screening era.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American journal of diseases of children · 1949 · 24 citations
END RESULTS IN TREATMENT OF CONGENITAL HYPOTHYROIDISM
AbstractTHIS paper reports the results of treatment of patients with congenital hypothyroidism over a period of thirteen to twenty-three years. Emphasis has been placed on their mental development and on their physical, behavioral, educational and socioeconomic progress. In the treatment of a patient having a chronic disorder, an important consideration is his restoration to maximum usefulness so that he may take his proper place in society. In congenital hypothyroidism, for which specific therapy is available, it would appear that this goal should not be difficult to accomplish. As far as the patient's physical development is concerned, such a result is usually achieved. However, it is the opinion of many investigators that even after prolonged and apparently adequate treatment the mental attainments of the congenitally hypothyroid patient frequently leave much to be desired. This view was supported by Bruch and McCune<sup>1</sup>who after intensive longitudinal studies on 23 children with
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.
Arquivos Brasileiros de Endocrinologia & Metabologia · 2012 · 8 citations · open access
Incidence of congenital hypothyroidism in the city of Uberaba/Minas Gerais and etiological evaluation of the affected subjects
AbstractOBJECTIVE: The objective of this study was to determine the incidence and etiology of congenital hypothyroidism (CH) in Uberaba, MG. SUBJECTS AND METHODS: From 2001 to 2010, by reviewing patient files from a public reference outpatient unit. The screening program covered 88% of live-born children. RESULTS: CH was diagnosed in 16 children, representing an incidence of 1:2,017 live-born children screened. The etiological evaluation was done in 15 children and revealed seven cases of thyroid dysgenesis, seven of dyshormonogenesis, and one case of transient hypothyroidism. One child moved away from the state before etiological investigation was carried out. CONCLUSION: We concluded that both the incidence of CH and of dyshormonogenesis as the main causes of CH were increased in the investigated region, but molecular studies are necessary for a better definition of etiology.
Journal of the Pakistan Medical Association · 2020 · 1 citations · open access
Insilico study of genes involved in Congenital Hypothyroidism.
AbstractOBJECTIVE: To study the orthologs of the five genes of congenital hypothyroidism NIS, PAX8, DUOX2, FOXE1, NKX2-1 that are involved in the development of the thyroid gland. METHODS: The study was conducted at INMOL Cancer Hospital, Lahore in September 2017 and comprised of finding gene orthologs, phylogenetic tree and domains of NIS, PAX8, DUOX2, FOXE1, NKX2-1 which were studied using different bioinformatics tools, including FASTA, BLAST, ENSEMBL, UniProt, MultiAlin, to find out the important domains involved in the mutations of these genes. RESULTS: Genes showed consensus sequence / motifs involved in congenital hypothyroidism. Phylogenetic results showed that these genes shared some common motifs. Phylogenetic trees revealed sub-clusters with high protein homology. CONCLUSIONS: Genes involved in congenital hypothyroidism were found to have a consensus sequence motifs.
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.
