DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for imperforate anus — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleImperforate anus maps to a 5-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 imperforate anus 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
mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) — MAP4K4 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 3-chlorophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4OBO · 2.1 Å · ligand 6-(3-chlorophenyl)quinazolin-4-amine (2QV). Experimental structure, not a prediction.
What the evidence adds up to
Infracoccygeal transperineal ultrasound was tested in 14 neonates with imperforate anus before corrective surgery. In 10 neonates a low-type imperforate anus was correctly diagnosed; the puborectalis muscle appeared as a hypoechoic U-shaped band and the distal rectal pouch passed through it. In four neonates with high-type imperforate anus the puborectalis muscle was not identified. The study concluded that this ultrasound approach enables determination of the type of imperforate anus, but no survival or response rates are reported because this is a diagnostic imaging study, not a treatment trial.
Sixteen patients with imperforate anus and chronic faecal incontinence were treated with either an artificial bowel sphincter (11 patients) or a gracilis neosphincter (5 patients) between 1995 and 2000. Mean follow-up was 1.7 years. The mean incontinence score fell from 18.5 to 7.5 in the artificial bowel sphincter group (P < 0.01) and from 17.4 to 9.4 in the gracilis neosphincter group (P = 0.06). Quality of life scores improved in both groups, but the improvement in the gracilis neosphincter group did not reach statistical significance for all scales. Eight complications occurred in six patients (50%), including faecal impaction, device migration, and wound infection; no devices were explanted. Resting and squeeze pressures increased significantly only in the artificial bowel sphincter group. The authors considered both techniques efficient, but the gracilis neosphincter results were less robust.
A single Korean family with six members affected by imperforate anus across three generations was studied by whole exome sequencing. A missense mutation in the EBF2 gene (c.215C > T; p.Ala72Val) was found to segregate completely with the disease. The mutation is evolutionarily conserved and predicted to be functionally damaging. No other families or larger cohorts have been reported, so this finding remains limited to one pedigree.
What is still missing is any drug treatment for imperforate anus. The surgical studies are small and uncontrolled, with short follow-up and a high complication rate. The genetic finding has not been replicated in other populations, and no functional studies in animal models or cell systems are reported. No trial design, patient stratification strategy, or funding for a pharmacological approach exists.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Radiology · 2003 · 37 citations
Imperforate Anus: US Determination of the Type with Infracoccygeal Approach
AbstractPURPOSE: To assess the usefulness of infracoccygeal transperineal ultrasonography (US) in differentiation between high- and low-type imperforate anus. MATERIALS AND METHODS: Infracoccygeal US was prospectively performed with a 7-10-MHz linear-array transducer prior to corrective surgery in 14 neonates with imperforate anus. The approach site was just inferior to the coccyx and posterior to the anus. Transverse images of the anorectal area were obtained. The puborectalis muscle was identified, and the relationship between the puborectalis muscle and the distal rectal pouch was evaluated. US findings were compared with surgical findings. RESULTS: In 10 neonates, a low-type imperforate anus was correctly diagnosed at infracoccygeal US. In those with low-type imperforate anus, the puborectalis muscle was seen as a hypoechoic U-shaped band (n = 10), and the distal rectal pouch passed through the puborectalis muscle (n = 10). In four neonates with high-type imperforate anus, the puborectalis muscle was not identified (n = 4). CONCLUSION: Infracoccygeal transperineal US enables the determination of the type of imperforate anus.
Diseases of the Colon & Rectum · 2004 · 36 citations
New Surgical Options for Fecal Incontinence in Patients With Imperforate Anus
AbstractINTRODUCTION: Anorectal malformations are among the various etiologic factors causing fecal incontinence. Patients with imperforate anus are difficult to treat, specifically those with high lesions. The artificial bowel sphincter and electrically stimulated gracilis neosphincter are two relatively new techniques that have been used for the treatment of patients with severe refractory fecal incontinence. The aim of this study was to evaluate the results of these technologies in the treatment of patients with chronic fecal incontinence due to imperforate anus. METHODS: All patients with imperforate anus who had fecal incontinence and underwent either the artificial bowel sphincter procedure or the gracilis neosphincter procedure between February 1995 and December 2000 were evaluated. Preoperative and postoperative incontinence score (Cleveland Clinic Florida Incontinence Score; 0 = perfect continence; 20 = complete incontinence), quality of life, (Fecal Incontinence Quality of Life Scale, 29 items forming 4 scales), and manometric sphincter pressure results were compared. RESULTS: Eleven patients had artificial bowel sphincter and five had the gracilis neosphincter (one nonstimulated) procedure. There were 11 males and 5 females of a mean age of 25.3 (range, 15-45) years. The mean follow-up time was 1.7 years (5 months to 5.7 years). Eight (50 percent) complications occurred in six patients, including three with fecal impaction (all artificial bowel sphincter), three with device migration (two gracilis neosphincter, one artificial bowel sphincter), and two patients with concomitant wound infection (one gracilis neosphincter, one artificial bowel sphincter); no patients had the devices explanted. Fourteen patients had manometric data (10 artificial bowel sphincter and 4 gracilis neosphincter) available. The overall incontinence score decreased from a preoperative mean of 18.5 to a postoperative mean of 7.5 in the artificial bowel sphincter group (P < 0.01) and from 17.4 to 9.4 in the gracilis neosphincter group (P = 0.06). All four Fecal Incontinence Quality of Life scales increased in both the artificial bowel sphincter (lifestyle and depression/self-perception, P = 0.02; coping/behavior and embarrassment, P = 0.03) and the gracilis neosphincter (lifestyle and coping, P = 0.06; depression and embarrassment, P = 0.05) patients. As well, the mean resting and squeeze pressures increased with both techniques (artificial bowel sphincter: P = 0.008 and P = 0.02, respectively; gracilis neosphincter: P = 0.4 and P = 0.1, respectively). All results were statistically significant in the artificial bowel sphincter group. CONCLUSIONS: Artificial bowel sphincter and gracilis neosphincter are efficient methods to treat patients with imperforate anus. These techniques should be considered for patients with imperforate anus and severe fecal incontinence.
American Journal of Medical Genetics Part A · 2018 · 4 citations
A missense mutation in <i>EBF2</i> was segregated with imperforate anus in a family across three generations
AbstractThe etiology of imperforate anus, a major phenotype of anorectal malformation (ARM), is still unknown and not a single gene has been reported to be associated with it. We studied a Korean family with six affected members with imperforate anus across three generations by whole exome sequencing and identified a missense mutation in the EBF2 gene (c.215C > T; p.Ala72Val). This mutation is completely segregated with the disease phenotype in the family and is evolutionarily highly conserved among diverse vertebrates. Also, this mutation was predicted to be functionally damaging. These results support that missense mutation in the EBF2 c.215C > T (p.Ala72Val) is very likely to contribute to the pathogenesis of ARM in this family.
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.
