DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Bartter disease type 3 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBartter disease type 3 maps to a 2-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 bartter disease type 3 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.
What the evidence adds up to
Bartter syndrome type 3 is caused by mutations in the CLCNKB gene. In a 2022 study of 21 children from 20 families, nine different CLCNKB mutations were found in ten patients, five of them novel. The same study reported that patients with classic Bartter syndrome (which includes type 3) had significantly lower mean plasma potassium and chloride concentrations at diagnosis compared to those with the antenatal form. Growth failure was the most frequent complaint across the whole cohort, and the median age at diagnosis was 8 months.
Treatment in a 1999 series of 13 Kuwaiti children consisted of supplemental potassium, spironolactone, and a prostaglandin synthetase inhibitor (indomethacin or aspirin) given sequentially. After indomethacin therapy, significant catch-up growth was recorded in four patients and increases in serum potassium in eight patients. One patient died of severe pneumonia with respiratory failure from hypokalemic myopathy. The estimated incidence in that population was 1.7 per 100,000 live births, with consanguinity in 69% and a family history in 54% of cases.
A 2023 systematic review of case reports and case series confirmed that Bartter syndrome is a rare autosomal recessive disorder with a wide range of signs and symptoms, and that five genetic types have been identified. A single 2023 case report described a 23-year-old man with adult-onset disease who responded well to conservative management, but no specific drug or regimen was detailed.
What remains missing is prospective trial data comparing treatment regimens, long-term outcome studies that track renal function and growth into adulthood, and any evidence that genetic subtyping (including CLCNKB mutations) guides therapy. No drug has been tested in a controlled trial for Bartter syndrome type 3 specifically.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Antenatal Bartter syndrome with sensorineural deafness: refinement of the locus on chromosome 1p31
AbstractBACKGROUND: Recently a locus for antenatal Bartter syndrome associated with sensorineural deafness was mapped to human chromosome 1p31 in a single consanguineous Bedouin family (Brennan et al. Am J Hum Genet 1998; 62: 355-361). METHODS: By haplotype analysis we demonstrate linkage to this locus in nine consanguineous families with antenatal Bartter syndrome associated with sensorineural deafness. RESULTS: The critical interval compatible with linkage was refined to 4.0 cM by two novel recombinational events with markers D1S2661 and D1S475. CONCLUSION: We thereby confirmed this gene locus and distinguished this clinical subtype from other variants of Bartter syndrome as a new disease entity.
Bartter's syndrome in Arabic children: review of 13 cases
AbstractBACKGROUND: Bartter's syndrome (BS) is an inherited disease of renal potassium wasting characterized by hypokalemic alkalosis, normal blood pressure, vascular insensitivity to pressor agents and elevated plasma concentrations of renin and aldosterone. It is caused by generalized hyperplasia of the juxtaglomerular apparatus at the site of renin production caused by mutations in the Na-K-2Cl cotransporter gene, NKCC2. The objective of our study is to establish the prevalence and incidence of BS in Kuwait and to assess treatment modalities for it. METHODS AND RESULTS: Bartter's syndrome was diagnosed in 13 Kuwaiti children over a 14 year period (1981-1995) with the estimated incidence of 1.7/100,000 live births. The mean age at diagnosis was 9.3 months (range 2-32 months). There were five males and eight females (ratio 1:1.6). The mean duration of follow up was 5.6 years (1-14 years). Both consanguinity and familial history among our patients were high (69 and 54%, respectively). All patients had hypokalemia, hypochloremia with metabolic alkalosis, hyperreninemia and were normotensive. Clinical presentation was essentially similar to that in other series. Eleven patients (85%) had growth failure, two had nephrocalcinosis (15%) and one had renal failure. All patients were treated with supplemental potassium, an aldosterone antagonist (spironolactone) and a prostaglandin synthetase inhibitor (indomethacin or aspirin) sequentially. Significant catch-up of growth (four patients) and increases in serum potassium (eight patients) were recorded after administration of indomethacin therapy. One patient died of severe pneumonia with respiratory failure from hypokalemic myopathy. Clinical presentation, inheritance, complications and therapy of BS are briefly discussed. CONCLUSION: Bartter's syndrome is a rare disease, but should be considered in the differential diagnosis of other disorders with growth failure and/or hypokalemia. Early diagnosis, close follow up and compliance with treatment may lead to appropriate growth and development.
Journal of Internal Medicine · 1989 · 10 citations
Bartter's syndrome—treatment with potassium, spironolactone and ACE‐inhibitor
AbstractThe treatment of Bartter's syndrome is fraught with difficulties, and there is no consensus concerning the pathogenetic mechanisms involved. Potassium depletion with hypokaliaemia is a dominant feature of the syndrome. In this case history, a 42-year-old woman suffering from Bartter's syndrome did not improve on several therapeutic trials. An impressive progress was noted, however, after intensive potassium repletion with subsequent potassium/spironolactone/ACE-inhibitor treatment. After 24 months her condition was unchanged with normal and stable Se-potassium concentration.
The Turkish Journal of Pediatrics · 2022 · 4 citations · open access
Phenotypic and genotypic characteristics of children with Bartter syndrome
AbstractINTRODUCTION: Bartter syndrome (BS) is a group of autosomal-recessive tubular disorders and it is classified into five genetic subtypes. BS can also be classified by phenotype (antenatal, classic). Patients with mutations in the same gene can present different phenotypes. In the present study, target gene sequencing was performed to evaluate the genotype-phenotype relationship. METHODS: Biochemical, clinical and renal ultrasonography results were collected at presentation and the last clinic visit. Genetic analyses were performed. The findings of patients with classical BS (cBS) and antenatal BS (aBS) at presentation and the last visit were compared. RESULTS: Our study included 21 patients (12 female, 57.1%) from 20 families with BS. The median age at diagnosis was 8 months and the median follow-up period was 39 months. The most frequent complaint was growth failure. We have found 18 different types of mutations in four genes, including nine in the CLCNKB gene, seven in the SLCA12A1 gene, one in the KCNJ1 gene and one in the BSND gene. In ten patients, nine different types of CLCNKB gene mutations were detected, five of them were novel. Seven different mutations in the SLC12A1 gene were detected in eight patients, five of them were novel. Compared to patients with aBS and cBS, prematurity was significantly higher in the group with aBS. Nephrocalcinosis was present in only one patient with cBS, all the ten hypercalciuric patients with aBS had nephrocalcinosis at the time of diagnosis and the last visit. The mean height standard deviation score (SDS) of patients with aBS were significantly lower than the cBS group at the time of presentation. The mean weight SDS at the time of presentation was worse in patients with aBS than in patients with cBS. The mean plasma potassium and chloride concentrations were significantly lower in the patients with cBS at the time of diagnosis. CONCLUSIONS: This investigation revealed the mutation characteristics and phenotype-genotype relationship of our patients and provided valuable data for genetic counseling.
Internal Medicine · 2001 · 3 citations · open access
Gitelman's Syndrome First Diagnosed as Bartter's Syndrome.
AbstractA 29-year-old man, who had been treated with potassium, spironolactone and indomethacin for over 9 years, was admitted because of nausea, vomiting, diarrhea and tetany manifestation. At the age of 20, he had been diagnosed as having Bartter's syndrome according to the criteria of the Japanese Ministry of Health and Welfare. Findings on admission were hypokalemia, hypomagnesemia and hypocalciuria. Renal distal fractional reabsorption rates of sodium, chloride and calcium were markedly decreased by administration of furosemide but there was no obvious change with administration of thiazide. These findings indicate that the patient had Gitelman's syndrome rather than Bartter's syndrome.
Barw Medical Journal · 2023 · 0 citations · open access
Adult-Onset Bartter Syndrome: A Case Report
AbstractAbstract Introduction Bartter syndrome is a rare genetically inherited salt-wasting disorder that is typically seen in children and neonates with association to many morbidities. We present a case of Bartter syndrome in an adult who showed excellent response to treatment. Case presentation The patient was a 23-year-old male presenting with polyuria, polydipsia, nocturia, and fatigue, especially within the lower limbs for the last two years but no history of vomiting. He was clinically diagnosed with Bartter syndrome and received conservative management with a good response. Conclusion Bartter syndrome is a rare disease. It has a wide range of clinical presentations. It can be diagnosed clinically and confirmed by genetic testing. Conservative management has a good clinical outcome.
Kidney International Reports · 2023 · 0 citations · open access
WCN23-0181 CLINICAL PRESENTATION, EPIDEMIOLOGY, MANAGEMENT, AND FOLLOW-UP FOR PATIENTS DIAGNOSED WITH BARTTER SYNDROME: A SYSTEMATIC REVIEW OF CASE REPORTS AND CASE SERIES
AbstractBartter syndrome (BS) is a relatively new and rare inherited disease identified as autosomal recessive in nature and characterized by a defect in transport mechanisms in the thick ascending loop of Henle. It usually manifests as a hypokalemic metabolic alkalosis with occasional hypochloremic and hyponatremic presentations. BS is associated with a wide range of signs and symptoms. To date, five different types of BS have been identified. This systematic review was conducted to evaluate the clinical presentation, epidemiology, management, and follow-up of BS patients reported worldwide.
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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