DeCure for Autosomal dominant pseudohypoaldosteronism type 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant pseudohypoaldosteronism type 1 — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAutosomal dominant pseudohypoaldosteronism type 1 maps to a 4-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 autosomal dominant pseudohypoaldosteronism type 1 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
nuclear receptor subfamily 3 group C member 2 (NR3C2) — NR3C2 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 2,2-difluoro-3-hydroxypropyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4PF3 · 1.1 Å · ligand 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (HFN). Experimental structure, not a prediction.
What the evidence adds up to
The mineralocorticoid receptor gene (MLR) maps to chromosome 4q31.2 by in situ hybridisation, and a defect in this gene was proposed in 2008 as the likely cause of autosomal recessive pseudohypoaldosteronism. However, a 1985 report described a female infant with severe failure to thrive and vomiting, and evaluation of her extended family revealed many affected members with a wide range of clinical expression; the authors concluded the mode of inheritance was most likely autosomal dominant. Salt supplementation during infancy was effective in restoring normal growth, weight gain and serum electrolytes in that family. A 2024 case report states that pseudohypoaldosteronism type 1 is a rare congenital autosomal recessive disorder characterised by failure of receptor response to aldosterone, caused by mutation in the SCNN1A gene. That report describes a male infant with seizures, hyperkalaemia and failure to thrive diagnosed at day 6 of life. The baby required repeated correction for hyperkalaemia; exome sequencing showed a pathogenic mutation for cystic fibrosis and a recessive mutation for pseudohypoaldosteronism. The authors note that clinically the features of pseudohypoaldosteronism predominated over cystic fibrosis, and that both conditions may coexist.
No controlled trial of any drug for autosomal dominant pseudohypoaldosteronism type 1 is reported in these abstracts. The only intervention described is salt supplementation, which was effective in one 1985 family but no quantitative survival or response rates are given. The 2024 infant required repeated correction of hyperkalaemia, but no specific drug therapy is mentioned. The abstracts disagree on whether the condition is autosomal recessive or dominant, and the genetic basis remains inconsistent: one abstract implicates MLR, another SCNN1A, and the 1985 report predates molecular confirmation.
What is still missing is a clear, consistent genetic definition of the autosomal dominant form, any prospective trial of a targeted therapy, and patient stratification by genotype. No drug repurposing data exist in these abstracts, and no survival or response numbers are provided beyond anecdotal improvement with salt in one family.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cytogenetics and Cell Genetics · 2008 · 36 citations
The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2
AbstractThe gene for the human mineralocorticoid receptor (MLR) was previously localized to chromosome 4. Here, we have localized this gene to 4q31.2 by in situ hybridization. This precise mapping of MLR will assist in the linkage analysis and genetic characterization of pseudohypoaldosteronism, an autosomal recessive disorder which likely results from a defect in the MLR gene.
Pseudohypoaldosteronism in a Female Infant and Her Family: Diversity of Clinical Expression and Mode of Inheritance
AbstractPseudohypoaldosteronism was diagnosed in an infant that clinically presented severe failure to thrive and vomiting. Evaluation of her extended family revealed many other affected family members with a vast range of clinical expression. The mode of inheritance is most likely autosomal dominant. Salt supplementation during infancy was effective in restoring normal growth, weight gain and serum electrolytes.
An unusual case of Pseudohypoaldosteronism coexisting with cystic fibrosis
AbstractPseudohypoaldosteronism type 1 is a rare congenital autosomal recessive disorder, characterised by failure of receptor response to aldosterone. It is caused by mutation in SCNN1A gene with clinical features like failure to thrive in infancy, hyponatraemia, hyperkalaemia and metabolic acidosis. We present a male infant with seizures, hyperkalaemia and with failure to thrive, diagnosed at day 6 of life. The baby required repeated correction for hyperkalaemia; hence, after ruling out treatable causes for hyperkalaemia, exonerated sequencing was done which showed pathogenic mutation for cystic fibrosis and recessive mutation for pseudohypoaldosteronism. But the child was clinically in favour of pseudohypoaldosteronism. Hence, features of pseudohypoaldosteronism predominate cystic fibrosis; they both may coexist.
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.
