DeCure for Generalized juvenile polyposis/juvenile polyposis coli
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for generalized juvenile polyposis/juvenile polyposis coli — 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 moduleGeneralized juvenile polyposis/juvenile polyposis coli 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 generalized juvenile polyposis/juvenile polyposis coli 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
SMAD family member 4 (SMAD4) — SMAD4 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9HZA · 2.03 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
Juvenile polyposis syndrome (JPS) is an autosomal dominant condition that produces hamartomatous polyps in the gastrointestinal tract and carries an increased risk of gastrointestinal malignancy. Disease-causing variants in BMPR1a or SMAD4 account for 45–60% of JPS cases, with BMPR1a variants alone accounting for 17–38% of cases. A 2024 literature review identified 211 distinct disease-causing variants in BMPR1a, drawn from published studies and the LOVD and ClinVar databases. These included missense, nonsense, frameshift, and large deletions across all functional domains of the gene. No specific genotype–phenotype correlation could be established for BMPR1a by variant type or functional domain. Unlike SMAD4 carriers, the review found no reports of gastric polyposis or gastric malignancy in BMPR1a carriers; colonic polyposis and colorectal malignancy occurred in carriers of either gene. The authors therefore proposed that BMPR1a carriers should only require surveillance for colorectal polyps and malignancy, and that gastric surveillance may be unnecessary. Patients with contiguous deletion of PTEN and BMPR1a can present with a severe infantile form of JPS involving gastrointestinal bleeding, diarrhoea, exudative enteropathy, and rectal prolapse.
A 1998 case report described a patient with juvenile polyposis who developed multiple and rapid recurrences of mixed polyps in an ileoanal pouch after restorative proctocolectomy. Despite regular surveillance and polypectomies, extensive serrated polyps recurred, the pouch could never be cleared, and it was surgically excised. The authors noted that mixed juvenile polyposis may affect any level of the gastrointestinal tract, including the ileal pouch and any rectal remnant.
The 2018 ESPGHAN Position Paper on juvenile polyposis in children and adolescents noted that most published studies are descriptive or retrospective. After applying a modified GRADE system, many of the recommendations are based on expert opinion rather than high-quality evidence. The paper provides a guide for diagnosis, assessment, and management, and calls for international collaboration and prospective patient registries to advance understanding of the condition.
What remains missing are prospective, multicentre trials that could provide reliable data on natural history and optimal surveillance intervals. No randomised controlled trials have tested whether different endoscopic schedules or chemopreventive strategies alter outcomes in JPS. Patient stratification by specific gene variant is not yet possible for BMPR1a, and the evidence base for surveillance recommendations remains largely observational and expert-derived.
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 · 2018 · 104 citations
Management of Juvenile Polyposis Syndrome in Children and Adolescents
AbstractThe European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Polyposis Working Group developed recommendations to assist clinicians and health care providers with appropriate management of patients with juvenile polyposis. This is the first juvenile polyposis Position Paper published by ESPGHAN with invited experts. Many of the published studies were descriptive and/or retrospective in nature, consequently after incorporating a modified version of the GRADE system many of the recommendations are based on expert opinion. This ESPGHAN Position Paper provides a guide for diagnosis, assessment, and management of juvenile polyposis syndrome in children and adolescents, and will be helpful in the appropriate management and timing of procedures in children and adolescents. The formation of international collaboration and consortia is proposed to monitor patients prospectively to advance our understanding of juvenile polyposis conditions.
Diseases of the Colon & Rectum · 1998 · 3 citations
Pouch excision for recurrent serrated adenomas following restorative proctocolectomy for juvenile polyposis
AbstractPURPOSE: The study contained herein was undertaken to report the case of a patient with juvenile polyposis in whom multiple and rapid recurrence of mixed polyps, with progressive predominance of the adenomatous component, developed in a diverted ileoanal pouch. METHODS: The case of this patient with juvenile polyposis was reviewed. Despite regular surveillance and polypectomies, extensive and multiple recurrences of serrated polyps developed. RESULTS: Because the pouch was never cleared of polyps, a compromise to remove the pouch was decided on. Such a case has not been reported previously. CONCLUSION: Mixed juvenile polyposis may affect any level of the gastrointestinal tract. The ileal pouch and any rectal remnant may incidentally need surgical excision.
Genotype–phenotype correlation of BMPR1a disease causing variants in juvenile polyposis syndrome
AbstractAbstract Background Juvenile Polyposis Syndrome (JPS) is an autosomal dominant condition with hamartomatous polyps in the gastrointestinal tract, associated with an increased risk of gastrointestinal malignancy. Disease causing variants (DCVs) in BMPR1a or SMAD4 account for 45–60% of JPS cases, with BMPR1a DCVs accounting for 17–38% of JPS cases. Within those with either a BMPR1a or SMAD4 DCV, there is phenotypic variability in location of polyps, risk of malignancy and extra-intestinal manifestations with limited published reports of gene-phenotype association or genotype–phenotype correlation. We aimed to identify any gene-phenotype association or genotype–phenotype correlation in BMPR1a to inform surveillance recommendations, and gene-specific modification to the ACMG classification of pathogenicity of DCVs. Methods A literature search was performed through EMBASE, MEDLINE and PubMed. Studies that were included explored BMPR1a DCV-related JPS or contiguous deletion of PTEN and BMPR1a. Data was also drawn from the BMPR1a specific databases on LOVD and ClinVar. Results There were 211 DCVs in BMPR1a identified, 82 from patients with JPS in the literature, and 17 from LOVD and 112 from ClinVar classified as pathogenic or likely pathogenic. These included missense, nonsense and frameshift variants and large deletions, occurring across all functional domains of the gene. Unlike in SMAD4 carriers, gastric polyposis and malignancy were not identified in our review in BMPR1a carriers, but colonic polyposis and malignancy occurred in carriers of either BMPR1a or SMAD4 DCVs. Those with contiguous deletion of PTEN and BMPR1a can present with JPS of infancy, with a severe phenotype of GI bleeding, diarrhoea, exudative enteropathy and rectal prolapse. No specific BMPR1a genotype–phenotype correlation could be ascertained including by variant type or functional domain. Conclusion Phenotypic characteristics cannot be used to inform variant location in BMPR1a. However, the phenotypic characteristics of BMPR1a DCV carriers, being almost exclusively related to the colon and rectum, can assist in pathogenicity assessment of BMPR1a variants. Given these findings, we propose that carriers of BMPR1a DCVs should only require surveillance for colorectal polyps and malignancy, and that surveillance for gastric polyps and malignancy may be unnecessary. However variant location within BMPR1a does not support differential surveillance recommendations.
Genotype–phenotype correlation of BMPR1a disease causing variants in juvenile polyposis syndrome
AbstractAbstract Background Juvenile Polyposis Syndrome (JPS) is an autosomal dominant condition with hamartomatous polyps in the gastrointestinal tract, associated with an increased risk of gastrointestinal malignancy. Disease causing variants (DCVs) in BMPR1a or SMAD4 account for 45–60% of JPS cases, with BMPR1a DCVs accounting for 17–38% of JPS cases. Within those with either a BMPR1a or SMAD4 DCV, there is phenotypic variability in location of polyps, risk of malignancy and extra-intestinal manifestations with limited published reports of gene-phenotype association or genotype–phenotype correlation. We aimed to identify any gene-phenotype association or genotype–phenotype correlation in BMPR1a to inform surveillance recommendations, and gene-specific modification to the ACMG classification of pathogenicity of DCVs. Methods A literature search was performed through EMBASE, MEDLINE and PubMed. Studies that were included explored BMPR1a DCV-related JPS or contiguous deletion of PTEN and BMPR1a. Data was also drawn from the BMPR1a specific databases on LOVD and ClinVar. Results There were 211 DCVs in BMPR1a identified, 82 from patients with JPS in the literature, and 17 from LOVD and 112 from ClinVar classified as pathogenic or likely pathogenic. These included missense, nonsense and frameshift variants and large deletions, occurring across all functional domains of the gene. Unlike in SMAD4 carriers, gastric polyposis and malignancy were not identified in our review in BMPR1a carriers, but colonic polyposis and malignancy occurred in carriers of either BMPR1a or SMAD4 DCVs. Those with contiguous deletion of PTEN and BMPR1a can present with JPS of infancy, with a severe phenotype of GI bleeding, diarrhoea, exudative enteropathy and rectal prolapse. No specific BMPR1a genotype–phenotype correlation could be ascertained including by variant type or functional domain. Conclusion Phenotypic characteristics cannot be used to inform variant location in BMPR1a. However, the phenotypic characteristics of BMPR1a DCV carriers, being almost exclusively related to the colon and rectum, can assist in pathogenicity assessment of BMPR1a variants. Given these findings, we propose that carriers of BMPR1a DCVs should only require surveillance for colorectal polyps and malignancy, and that surveillance for gastric polyps and malignancy may be unnecessary. However variant location within BMPR1a does not support differential surveillance recommendations.
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.
