DeCure for Diabetes insipidus, nephrogenic, autosomal
DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for diabetes insipidus, nephrogenic, autosomal — 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 insipidus, nephrogenic, autosomal 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 insipidus, nephrogenic, autosomal 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
aquaporin 2 (AQP2) — AQP2 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 8GCL · 2.89 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A Belgian kindred with X-linked congenital nephrogenic diabetes insipidus (CNDI) was found to carry a novel missense mutation (1454C>A) in exon 3 of the AVPR2 gene, predicting a Ser329Arg substitution. The two affected brothers had partial resistance to arginine-vasopressin (AVP). Under basal conditions, their 24-hour urine volumes were 5.5 litres (229 ml/kg) and 3.5 litres (192 ml/kg), with urine osmolalities of 78 and 90 mosm/kg, and plasma AVP levels of 13.5 and 19.0 pg/ml. During fluid deprivation, urine osmolalities rose to 573 and 720 mosm/kg while plasma AVP remained nearly unchanged at 13.6 and 8.8 pg/ml. Infusion of AVP produced urine osmolalities of 523 and 623 mosm/kg at plasma AVP levels of 58 and 42 pg/ml. Infusion of desmopressin (dDAVP) had a similar effect, but standard intranasal dDAVP treatment had no effect on urine output.
Familial central diabetes insipidus (CDI) is typically of late onset and slowly progressive during the first few years of life, in contrast to the severe dehydration seen soon after birth in patients with NDI. These differences in clinical presentation and genetic transmission have become partly explicable with the characterisation of molecular defects. A 2023 report describes a case of idiopathic partial central diabetes insipidus, noting that diabetes insipidus is a rare disorder caused either by antidiuretic hormone deficiency (central) or resistance to its action in the renal tubules (nephrogenic).
No treatment recommendations can be made from these abstracts. The 2007 study shows that standard intranasal dDAVP was ineffective in the partial NDI patients despite the hormone having some effect when infused. What remains missing is a trial design that tests alternative dosing or routes for dDAVP in partial NDI, and patient stratification by specific AVPR2 mutation to predict which individuals might respond to any intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Endocrinology · 2007 · 43 citations
Partial nephrogenic diabetes insipidus caused by a novel mutation in the AVPR2 gene
AbstractOBJECTIVE: To identify the molecular basis and clinical characteristics of X-linked congenital nephrogenic diabetes insipidus (CNDI) presenting with an unusual phenotype characterized by partial resistance to AVP. SUBJECTS: The proband was admitted at the age of 4 years with a history of polydipsia and polyuria since infancy. Initial clinical testing confirmed a diagnosis of diabetes insipidus (DI). Urine osmolarity rose during fluid deprivation and after 20 microg of intranasal desmopressin [1-deamino-8-D-arginine-vasopressin (dDAVP)]. A similar DI phenotype was found in his brother. METHODS: The coding regions of the AVP gene and the AVP receptor 2 (AVPR2) genes were sequenced in two affected and three unaffected family members. Clinical studies included a fluid deprivation test, intranasal dDAVP challenge, infusion of graded doses of dDAVP and AVP, and measurements of 24-h urine output before and at the end of a 7-day therapeutic trial of intranasal dDAVP. RESULTS: A novel missense mutation (1454C > A) in exon 3 of the AVPR2 gene predicting a Ser329Arg substitution was identified in the X-chromosome of the two affected brothers and in one of the X-chromosomes in the mother. The AVPR2 gene was normal in two unaffected siblings. Under basal conditions, the 24-h urine volumes of the two affected boys were 5.5 l (229 ml/kg) and 3.5 l (192 ml/kg), the urine osmolalities were 78 and 90 mosm/kg, and plasma AVP 13.5 and 19.0 pg/ml. Urine osmolalities increased to 573 and 720 mosm/kg while plasma AVP levels were practically unchanged, 13.6 and 8.8 pg/ml, during fluid deprivation. Infusion of AVP resulted in urine osmolalities of 523 and 623 mosm/kg at plasma AVP levels of 58 and 42 pg/ml. Infusion of dDAVP had a similar effect, while treatment with standard doses of intranasal dDAVP had no effect on urine output. DISCUSSION: The affected members of this Belgian kindred have CNDI with partial resistance to AVP caused by a mutation in the AVPR2 gene that differs from any of the six mutations reported previously to produce this phenotype. Because the resistance to AVP is partial, this form of CNDI can be difficult to distinguish by indirect diagnostic tests from partial pituitary and dipsogenic DI.
European Journal of Endocrinology · 1996 · 4 citations
Molecular pathology of familial central diabetes insipidus
AbstractDiabetes insipidus is caused by either the lack of arginine-vasopressin (AVP) in central diabetes insipidus (CDI) or the resistance to the action of this hormone in nephrogenic diabetes insipidus (NDI). While the causes of CDI and NDI are mostly acquired, a small percentage is hereditary in either a dominant (CDI) or recessive manner (NDI). Familial CDI is typically of late onset and slowly progressive during the first few years of life, in contrast to the frequently severe dehydration seen soon after birth in patients with NDI. These differences in the clinical presentation and the genetic mode of transmission have become at least partly explicable with the characterization of the molecular defects in patients with CDI and NDI.
AbstractABSTRACT Diabetes insipidus is a rare disorder characterized by the inability to concentrate urine, which results in hypotonic urine and increased urinary volume. It may occur because of antidiuretic hormone deficiency or resistance to its action in the renal tubules. When there is a deficiency in the synthesis of antidiuretic hormones, diabetes insipidus is called central; when there is resistance to its action in the renal tubules, it is said to be nephrogenic. We report a case of idiopathic partial central diabetes insipidus and highlight the management and treatment of the disease.
INDIGO (University of Illinois at Chicago) · 2023 · 0 citations · open access
Idiopathic partial central diabetes insipidus
AbstractABSTRACT Diabetes insipidus is a rare disorder characterized by the inability to concentrate urine, which results in hypotonic urine and increased urinary volume. It may occur because of antidiuretic hormone deficiency or resistance to its action in the renal tubules. When there is a deficiency in the synthesis of antidiuretic hormones, diabetes insipidus is called central; when there is resistance to its action in the renal tubules, it is said to be nephrogenic. We report a case of idiopathic partial central diabetes insipidus and highlight the management and treatment of the disease.
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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