DeCure for Congenital enteropathy due to enteropeptidase deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital enteropathy due to enteropeptidase deficiency — 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 enteropathy due to enteropeptidase deficiency 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 enteropathy due to enteropeptidase deficiency 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
transmembrane serine protease 15 (TMPRSS15) — TMPRSS15 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 8ZIY · 2.64 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1984 case report describes a child with primary enteropeptidase deficiency followed from birth to 18 months. Biochemical analysis of small intestinal biopsy and duodenal juice showed total absence of enteropeptidase activity. Proteolytic activity in native duodenal juice was very low, but normal levels could be induced in vitro by adding porcine enteropeptidase. The report gives no quantitative survival or response data for the patient.
Microvillus inclusion disease, a separate congenital enteropathy caused by mutations in myosin 5β, syntaxin-binding protein 2, or syntaxin 3, presents with intractable life-threatening watery diarrhea. In the early-onset form symptoms appear in the first days after birth; in the late-onset form at about 2 to 3 months. Patients cannot tolerate feedings and require continuous total parenteral nutrition. Mortality is extremely high in the early-onset type, with survival reported only in patients treated with small intestinal transplantation. The 2020 review provides no response rates or survival numbers beyond that statement.
Congenital tufting enteropathy, caused by mutations in the EpCAM gene, presents with intractable watery diarrhea, weight loss, malnutrition, and growth retardation in newborns. A 2024 report describes a Turkish neonate diagnosed by clinical signs and genetic analysis who was fed by total parenteral nutrition and a carbohydrate-poor formula. No survival or response data are given for that patient.
No drug treatment is described in any of these abstracts for any of the three enteropathies. What is missing for all of them is any controlled trial of a pharmacological intervention, any evidence that a drug can alter the course of disease, and any stratification of patients by genetic subtype that might identify a treatable subgroup.
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 Pediatric Gastroenterology and Nutrition · 1984 · 12 citations
Primary Intestinal Enteropeptidase Deficiency
AbstractA rare case of primary enteropeptidase deficiency is reported. Details are given of the initial clinical presentation, treatment, and response of the patient from birth to the age of 18 months. Biochemical analysis of a small intestinal biopsy and duodenal juice samples confirmed the total absence of enteropeptidase activity. Proteolytic activity was very low in native duodenal juice, but normal levels could be induced by activation in vitro with a small amount of porcine enteropeptidase.
Challenges of Microvillus Inclusion Disease in the NICU
AbstractMutations in the myosin 5β, syntaxin-binding protein 2, and syntaxin 3 genes lead to microvillus inclusion disease (MVID), an autosomal recessive congenital enteropathy. This rare disease is characterized by lack of microvilli on the surface of enterocytes in the small intestine, the presence of pathognomonic intracellular microvillus inclusions, and vesicular bodies within these enterocytes. This pathology leads to the characteristic intractable, life-threatening, watery diarrhea. In the more common early-onset form, affected patients present in the first few days after birth, whereas in the late-onset form, clinical manifestations appear at approximately 2 to 3 months of age. Genetic testing can confirm the diagnosis, but the infant's medical history, clinical presentation, and small intestinal biopsy results are strongly suggestive of the diagnosis. The prevalence of MVID is thought to be higher in countries with a high degree of consanguinity. Patients with MVID cannot tolerate feedings and require continuous total parenteral nutrition. Mortality is extremely high in the early-onset type with reports of survival in patients treated with small intestinal transplantation. Medical counseling for parents of infants with MVID needs to reflect our current understanding of the various genetic forms of this disease, the feasible management, and anticipated outcomes.
Gaziantep Islam Science and Technology University · 2024 · 1 citations · open access
A Novel Homozygote EpCAM Gene Mutation in Turkish Neonate with Tufting Enteropathy
AbstractCongenital tufting enteropathy is characterized by intractable watery diarrhea, weight loss, malnutrition and growth retardation in newborn. It is a rare autosomal recessive disorder which is caused by mutations in the gene encoding human epithelial cell adhesion molecule (EpCAM). The diagnosis is based on a combination of clinical signs, histological findings and genetic tests that identify a mutation in the EPCAM gene. We report a Turkish neonate with congenital tufting enteropathy presenting to the emergency department with severe watery diarrhea and weight loss. He was diagnosed as having congenital tufting enteropathy based on his clinical signs and genetic analysis. He was fed by total parenteral nutrition and carbohydrate-poor formula. Despite fact that it is often difficult to find the etiology of conditions that cause congenital diarrhea, clinical suspicion and genetic analysis might be helpful in making the diagnosis of congenital tufting enteropathy.
Journal of Pediatric Gastroenterology and Nutrition · 1984 · 1 citations
Primary Intestinal Enteropeptidase Deficiency
AbstractA rare case of primary enteropeptidase deficiency is reported. Details are given of the initial clinical presentation, treatment, and response of the patient from birth to the age of 18 months. Biochemical analysis of a small intestinal biopsy and duodenal juice samples confirmed the total absence of enteropeptidase activity. Proteolytic activity was very low in native duodenal juice, but normal levels could be induced by activation in vitro with a small amount of porcine enteropeptidase.
International Journal of Life Science and Pharma Research · 2022 · 0 citations · open access
Intestinal Enterokinase Deficiency in Pediatrics
AbstractAbstract: Congenital enteropeptidase deficiency (CEP), also known as enterokinase deficiency. CEP is an uncommon autosomal recessive genetic disorder mostly characterized by severe chronic diarrhoea after delivery, hypoproteinemia, and failure to grow. Enteropeptidase activity is anticipated to play a significant role in protein digestion. For growth and appropriate development in newborns with a congenital lack of the enzyme, pancreatic enzyme replacement treatment or an amino acid combination must be given. Only 13 cases of enterokinase insufficiency have been recorded since it was originally characterized in 1969. Couples should be informed that prenatal screening is an option and that EKD has a favourable prognosis. However, if an EKD patient is born, parents should be aware of the feeding issue and offer the proper pancreatic exocrine secretion medication. One research found that all patients had been diagnosed as newborns 25 years ago. Even when the pancreatic-enzyme replacement was stopped, they appeared to lead regular lives as adults, free of gastrointestinal issues and with normal body weight. This can be explained by the fact that trypsin, once liberated from its precursor, encourages additional trypsinogen activation in a positive-feedback manner. Better pharmaceutical preparations such as enteric-coated minimicrospheres and delayed-release capsules are used for better results as it maintains the enzyme and prevents its breakdown by stomach acidity. This review aims to summarise current knowledge of pathophysiology, causes, and treatment of Intestinal Enterokinase Deficiency in Pediatrics
Archivos Argentinos de Pediatria · 2014 · 0 citations · open access
Deficiencia de biotinidasa y malformación de anillo vascular. Reporte de un caso
AbstractBiotinidase deficiency is an autosomal recessive metabolic disorder that affects the cleavage of biotin. Family studies of the index case found that both parents are usually carriers and siblings have the altered gene, but only homozygotes have manifestations that vary depending on the deficiency grade. Mothers may have moderate deficiency and be asymptomatic; biotin deficiency in pregnant women causes defects in children. In a study, using human cells exposed to biotin deficiency, cell growth decreased contributing to the development of cleft palate. In newborns, biotinidase deficiency has been associated with VACTERL syndrome and annular pancreas. The case of an infant with biotinidase deficiency and congenital defect of the vascular ring is presented. This defect surrounds and compresses the trachea and esophagus, disturbing swallowing and breathing. Infant was supplemented with biotin and surgically intervened with excellent results.
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.
