DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Liddle syndrome — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLiddle syndrome maps to a 3-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 liddle syndrome 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
sodium channel epithelial 1 subunit alpha (SCNN1A) — SCNN1A 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 6WTH · 3.06 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Liddle syndrome is a tubulopathy with autosomal dominant inheritance, determined by mutations in the genes controlling the expression of β and γ subunits of epithelial sodium channels (ENaC) located on the apical membranes of connecting tubule and cortical collecting duct cells. The disease shows itself as volume-dependent, low-renin hypertension, hypokalaemia, and metabolic alkalosis. It is very rare and often manifests in childhood, but can be first noticed in adults or even elderly patients. In a 2001 study of a Chinese family, twelve members were recruited; two brothers had a clinical diagnosis of Liddle syndrome. Direct DNA sequencing of the last exon of the β ENaC gene (codons 513-673) revealed a missense mutation of CCC to CTC at codon 616 (Pro616) in four middle-aged men of the second generation and one young woman of the third generation. No mutation was found in the γ ENaC gene in any individual examined. The authors concluded that Pro616 is a critical amino acid for inhibition of sodium channel activity.
A 2018 study screened the C-terminus of SCNN1B and SCNN1G genes in a 19-year-old male patient with treatment-resistant hypertension and hypokalaemia, and his family members. A recurrent SCNN1B mutation, c.1853C>A (p.P618H), was detected in the proband, and family screening identified five additional heterozygous members. The diagnosis of Liddle syndrome was made in all affected individuals. A systematic review of 54 reported index cases found that early-onset hypertension, at age no more than 30 years, was a common feature. The authors recommended genetic screening for Liddle syndrome in hypertensive subjects with early penetrance, perhaps under 30 years, after excluding common secondary causes of hypertension.
Treatment described in a 2009 review includes organic salts in the diet, potassium salt replacement therapy, and potassium-sparing diuretics such as amiloride and triamterene. No controlled trial data on these treatments are provided in the abstracts. The 2018 study notes that phenotypic variability makes identification difficult, leading to misdiagnosis and severe complications at early age. What remains missing is prospective data on how genetic screening changes long-term outcomes, standardised diagnostic criteria that account for variable penetrance, and any trial comparing treatment regimens in mutation-confirmed patients.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Hypertension · 2001 · 30 citations
Diagnosis of Liddle syndrome by genetic analysis of β and γ subunits of epithelial sodium channel – a report of five affected family members
AbstractOBJECTIVE: To screen the gene mutation in beta and gamma subunits of the epithelial sodium channel (ENaC) of a Chinese family, some of whose members are clinically diagnosed as suffering from Liddle syndrome. METHODS: Twelve family members were recruited to the study. Among them, two brothers had been clinically diagnosed as suffering from Liddle syndrome. Peripheral blood samples were collected from all members of the family and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction (PCR) was used for amplifying the last exon of beta (codon 513-673) and gamma (codon 503-632) subunits of the ENaC gene. PCR products were purified and subjected to a direct DNA sequence analysis. RESULTS: Genetic analysis of the beta ENaC gene revealed a missense mutation of CCC to CTC at codon 616 in four middle-aged men of the second generation and one young woman of the third generation. There was no mutation of the gamma ENaC gene in any of the individuals examined. CONCLUSION: Through direct DNA sequencing analysis, we diagnosed the disease present in five members of a Chinese family as Liddle syndrome, and excluded it in some other young offspring suffering from the monogenic disease. Our results provide further evidence that Pro616 is a critical amino acid that has a key role in the inhibition of sodium channel activity.
Редкие заболевания в практике "взрослого" нефролога: состояния, ассоциированные с гипокалиемией. Сообщение II. Синдром Лиддля
AbstractThe Liddle syndrome was described in 1963. And according to the modern views is a tubolopathy with autosomal dominant inheritance. It is determined by the mutation of the genes, controlling the expression of β and γ-subunits of epithelial sodium channels (ENaC), which are mostly located on the apical membranes of the main cells connecting tubules and cortical collecting ducts. The disease is very rare and shows itself in a volume-dependant, low rennin hypertension, hypokaliemia, and metabolic alkolosis. The Liddle syndrome quite often manifestoes in the childhood, but can be primary noticed in adults even in elderly patients. As a treatment organic salts in the ration, potassium salt substitutive therapy and potassium saving diuretics (amylorid, triamteren) are used.
Genetic screening of <i>SCNN1B</i> and <i>SCNN1G</i> genes in early-onset hypertensive patients helps to identify Liddle syndrome
Abstract<i>Background</i>: Liddle syndrome is an autosomal dominant form of monogenic hypertension. Phenotypic variability makes it difficult to identify patients with Liddle syndrome, resulting in misdiagnosis and severe complications at early age. <i>Objectives</i>: To identify mutation in <i>SCNN1B</i> and <i>SCNN1G</i> genes in an adolescent with suspicious Liddle syndrome and his family members and to explore the screening target subjects of Liddle syndrome. <i>Methods</i>: Genetic analysis of the C-terminus of <i>SCNN1B</i> and <i>SCNN1G</i> genes was conducted in an adolescent, with treatment-resistant hypertension and hypokalemia, who was suspected of having Liddle syndrome, and his family members. A Medline research of the reported cases with Liddle syndrome was also performed. <i>Results</i>: A recurrent <i>SCNN1B</i> mutation, c.1853C>A (p.P618H), was detected in the 19-year-old male patient, and family screening identified five additional members who were heterozygous for the mutation. The diagnosis of Liddle syndrome was made in all affected individuals. Despite the phenotypic variability, a systematic review of 54 reported index cases revealed the early-onset hypertension, aged no more than 30 years, as a common feature. <i>Conclusions</i>: Genetic screening for Liddle syndrome should be considered in hypertensive subjects with early penetrance, maybe no more than 30 years, after exclusion of common secondary causes of hypertension.
Genetic screening of <i>SCNN1B</i> and <i>SCNN1G</i> genes in early-onset hypertensive patients helps to identify Liddle syndrome
Abstract<i>Background</i>: Liddle syndrome is an autosomal dominant form of monogenic hypertension. Phenotypic variability makes it difficult to identify patients with Liddle syndrome, resulting in misdiagnosis and severe complications at early age. <i>Objectives</i>: To identify mutation in <i>SCNN1B</i> and <i>SCNN1G</i> genes in an adolescent with suspicious Liddle syndrome and his family members and to explore the screening target subjects of Liddle syndrome. <i>Methods</i>: Genetic analysis of the C-terminus of <i>SCNN1B</i> and <i>SCNN1G</i> genes was conducted in an adolescent, with treatment-resistant hypertension and hypokalemia, who was suspected of having Liddle syndrome, and his family members. A Medline research of the reported cases with Liddle syndrome was also performed. <i>Results</i>: A recurrent <i>SCNN1B</i> mutation, c.1853C>A (p.P618H), was detected in the 19-year-old male patient, and family screening identified five additional members who were heterozygous for the mutation. The diagnosis of Liddle syndrome was made in all affected individuals. Despite the phenotypic variability, a systematic review of 54 reported index cases revealed the early-onset hypertension, aged no more than 30 years, as a common feature. <i>Conclusions</i>: Genetic screening for Liddle syndrome should be considered in hypertensive subjects with early penetrance, maybe no more than 30 years, after exclusion of common secondary causes of hypertension.
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.
