DeCure for Congenital secretory chloride diarrhea 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital secretory chloride diarrhea 1 — 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 moduleCongenital secretory chloride diarrhea 1 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 congenital secretory chloride diarrhea 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
solute carrier family 26 member 3 (SLC26A3) — SLC26A3 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 oxldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8X1U · 2.21 Å · ligand OXALATE ION (OXL). Experimental structure, not a prediction.
What the evidence adds up to
Congenital secretory chloride diarrhea 1 is an autosomal recessive disease caused by mutations in the SLC26A3 gene, which encodes an intestinal Cl–/HCO3– exchanger. The defect leads to malabsorption of chloride in the ileum and colon. More than 250 cases had been reported by the early 21st century, mostly in Finland, Poland, Kuwait, and Saudi Arabia. The disease can be detected during pregnancy by polyhydramnios and dilated fetal intestinal loops on ultrasound. Most children are born prematurely. After birth, the main features are watery diarrhea, dehydration, failure to thrive, hypochloremia, hyponatremia, hypokalemia, and metabolic alkalosis. Fecal chloride excretion exceeds total sodium and potassium excretion. Diagnosis is based on detecting excessive chloride in the stool (90 mmol/L or higher) and confirmed by genetic analysis.
Treatment consists of potassium chloride and sodium chloride replacement therapy. This salt supplementation stops electrolyte disturbances, but diarrhea persists. With adequate treatment, patients now reach adulthood, but the long-term prognosis is unknown. One case report describes a girl treated with sodium chloride and potassium chloride who was observed for five years; her physical and psychomotor development corresponded to her age and she had no electrolyte abnormalities. Another report describes a Turkish neonate treated with salt supplements and lansoprazole. A 2013 report from Bangladesh discusses captopril and its effectiveness in two cases, but provides no concrete response rates or survival numbers for that intervention.
Delayed diagnosis is common. The abdominal distension and watery diarrhea can mimic intestinal obstruction or Hirschprung’s disease, leading to unnecessary surgical interventions that increase morbidity. Two of three patients in one case series underwent surgery for suspected obstruction before the correct diagnosis was made. A 2017 report describes five such cases in Saudi Arabia, where the incidence is 1/5000. A 2012 case describes a male newborn with a novel homozygous SLC26A3 mutation whose persistent diarrhea and electrolyte disturbances began only on day 8 of life, suggesting a variable clinical course that requires tight follow-up.
What is still missing are large prospective studies to establish long-term outcomes, standardised protocols for early diagnosis to prevent unnecessary surgery, and controlled trials of any drug beyond salt replacement — including captopril, for which no efficacy data from controlled studies are reported. Patient stratification by mutation type and age at diagnosis may clarify prognosis, but such data are not yet available.
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 Physiology-Cell Physiology · 1993 · 143 citations
Positive and negative regulation of chloride secretion in T84 cells
AbstractThis review discusses recent findings regarding the mechanisms and regulation of chloride secretion in the T84 cell line, a widely used model for the study of transepithelial chloride transport, the properties of the cystic fibrosis gene product (cystic fibrosis transmembrane conductance regulator), and the interactions of inflammatory cell types with the intestinal epithelium. First, I review the features of the chloride secretory mechanism in this cell line, both as originally described by Dharmsathaphorn and co-workers and as modified by more recent findings. Second, I cover what is known of the intracellular regulation of the secretory process. Third, I review the ways in which the cell line has been utilized to dissect pathways of immune-epithelial interactions that may contribute to the pathogenesis of inflammatory diarrhea. Finally, I suggest areas of investigation with this cell line that may prove ripe for further study. The physiological and pathophysiological implications of findings obtained with the cell line are also discussed.
Türk Pediatri Arşivi · 2018 · 6 citations · open access
SLC26A3 mutation in Turkish neonate and her sibling with congenital chloride diarrhea
AbstractCongenital chloride diarrhea is a rare cause of severe infantile diarrhea with excessive chloride excretion. Mutations in the SLC26A3 gene cause congenital chloride diarrhea. It generally becomes apparent in the neonatal period and is characterized by electrolyte imbalances, metabolic alkalosis, and failure to thrive. The diagnosis of congenital chloride diarrhea is based on detecting excessive chloride in the stool (90 mmol/L). We report a Turkish neonate with congenital chloride diarrhea whose sibling had the same disease. The newborn was born by cesarean delivery. Diarrhea, vomiting, and weight loss started soon after birth. She was diagnosed as having congenital chloride diarrhea based on its typical clinical signs and a high concentration of stool chloride and was confirmed by genetic analysis. She was treated by means of salt supplementations and lansoprazole. Family history may play an important role in the early diagnosis because the disease is inherited autosomal recessively.
Экспериментальная и клиническая гастроэнтерология · 2022 · 3 citations · open access
Congenital chloride diarrhea
AbstractCongenital chloride diarrhea is an autosomal recessive congenital disease caused by a mutation in the SLC26A3 gene mapped to chromosome 7 (locus 7q22-q31). At the beginning of the 21st century, more than 250 cases of congenital chloride diarrhea have been reported, mostly in Finland, Poland, Kuwait, and Saudi Arabia, single cases appear all over the world. SLC26A3 gene encodes an intestinal Cl–/HCO3 – exchanger, а defect of which causes malabsorption of Cl– in the ileum and colon. The disease can be revealed during pregnancy by polyhydramnios, dilated intestinal loops of the fetus on sonography.Most children are born prematurely. Visualization of distended bowel loops and the absence of meconium after birth often leads to unnecessary surgical intervention due to suspected intestinal obstruction or Hirschprung’s disease. The main features of the disease are watery diarrhea, dehydration, failure to thrive, hypochloremia, hyponatremia, hypokalemia and metabolic alkalosis. Fecal chloride excretion is higher than total sodium and potassium excretion. Treatment consists of potassium chloride and sodium chloride replacement therapy. Nowadays patients with adequate treatment reach adulthood but the long-term prognosis is unknown. Therapy stops electrolyte disturbances, but diarrhea persists. Since 2003, we have observed 3 patients with clinical signs of congenital chloride diarrhea with further confi rmation of a mutation in the SLC26A3 gene. All the children were born prematurely, the mothers had polyhydramnios during pregnancy, and the fetus had dilated bowel loops on ultrasound examination in utero. Two patients underwent surgical treatment because of suspected intestinal obstruction or Hirschsprung’s disease in early neonatal period. Before salt substitution therapy, all children had watery diarrhea, failure to thrive and delayed psychomotor development. We have been observing one of our patients for fi ve years from the moment of diagnosis until now. The girl receives therapy with sodium chloride and potassium chloride, her physical and psychomotor development corresponds to her age, there are no electrolyte abnormalities.
The Turkish Journal of Gastroenterology · 2017 · 2 citations · open access
Surgical consequences in infants with delayed diagnosis of congenital chloride diarrhea
AbstractDespite the usual typical presentation, congenital chloride diarrhea (CCD) poses multiple diagnostic challenges. It has an incidence of 1/5000 in Saudi Arabia. CCD can mimic intestinal obstruction and result in avoidable surgical interventions. Contributing factors are abdominal distension and the watery (urine-like) diarrhea that is often interpreted as delayed passage of meconium. Surgical interventions would unnecessarily increase the morbidity. Therefore, a high index of suspicion and educating neonatologists, general pediatricians, and pediatric surgeons regarding this diagnostic entity is essential. Here we describe five such cases.
Acta Paediatrica · 2012 · 2 citations · open access
Follow‐up of a child with congenital chloride diarrhoea caused by a novel mutation
AbstractUNLABELLED: Congenital chloride diarrhoea (CLD) is a rare autosomal recessive disease with chronic secretory diarrhoea and a need for lifelong salt replacement therapy. We describe a male newborn of consanguineous parents with CLD. Postnatally, frequent watery diarrhoea and electrolyte disturbances were noted from the day 8 of his life. At molecular level, a homozygous mutation was detected in the solute carrier family 26 member A3 gene (SLC26A3), confirming the clinical diagnosis of CLD. CONCLUSION: The relatively late onset of persistent clinical and laboratory signs may demonstrate a new clinical course of CLD. These findings support the need of a tight follow-up and monitoring if such a diagnosis is considered.
Indian Journal of Child Health · 2018 · 1 citations · open access
Congenital chloride diarrhea: A rare cause of recurrent polyhydramnios
AbstractCongenital chloride diarrhea (CCD) is a rare, inherited disorder. Our case was a preterm neonate who presented with severe watery diarrhoea since Day 2 of life. There was maternal history of polyhydramnios and dilated bowel loops. The diagnosis of CCD was confirmed by mutation analysis. The infant is 9 months corrected age, on salt and potassium supplementation, with age-appropriate milestones. The diagnosis of CCD must be made early to prevent life-threatening fluid and electrolyte imbalance.
Journal of Clinical Case Reports · 2013 · 0 citations · open access
Congenital Chloride Diarrhoea: First Time Diagnosis in Bangladesh and its Management Difficulties
AbstractCongenital Chloride Diarrhoea (CCD) is a form of autosomal recessive disorder which is presented by persistent chloride rich watery diarrhea from birth. Diagnosis of CCD is simple but it needs early prediction and clinical and laboratory evaluation. It can be tentatively made from the typical history of polyhydramnios in antenatal period, prematurity, and watery diarrhea from the beginning and then confirmed by the high fecal concentration of Cl-. Serum electrolyte and pH changes are not reliable diagnostic criteria. Without early intervention most of the children will die in infancy, rest will achieve failure to thrive, and psychomotor developmental delay. .Although congenital chloride diarrhoea has been reported worldwide, but in Bangladesh, we have no reported cases. Here we have discussed two cases of CCD with their diagnostic and management outcome and also discuses about captopril and its effectiveness. Early diagnosis and treatment are essential for normal growth, development, and prevention of other severe complications of congenital chloride diarrhea.
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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