DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Cornelia de Lange syndrome 6 — 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 moduleCornelia de Lange syndrome 6 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 cornelia de lange syndrome 6 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
ALF transcription elongation factor 4 (AFF4) — AFF4 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 ampdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4IMY · 2.94 Å · ligand ADENOSINE MONOPHOSPHATE (AMP). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 case report describes a 20-year-old male with Cornelia de Lange syndrome (CdLS) who was diagnosed with ulcerative colitis after presenting with bloody diarrhoea, abdominal pain, and 6 kg weight loss. He had a family history of ulcerative colitis in his mother. Initial treatment with oral mesalazine 3 g/day, mesalazine enema 4 g/day, and oral prednisolone 30 mg produced no response, mainly because the patient’s behavioural problems and poor compliance led him to avoid the medications by voluntary emesis. Infliximab was then given intravenously at 5 mg/kg as a loading dose at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks. The patient showed prompt clinical response and was in clinical remission at the time of reporting. This is the first reported case of CdLS coexisting with ulcerative colitis.
The 2010 symposium abstracts and the 2016 review provide no treatment data. The 2010 document is a programme listing talks on genetics and molecular biology, with no clinical results. The 2016 review states that CdLS causes severe growth retardation, cognitive impairment, characteristic facial and upper limb defects, and that research has focused on pathogenesis. The 2014 abstract notes that three mutations are known (NIPBL, SMC1A, SMC3) and that most cases are de novo, but gives no treatment information.
The 2013 case is a single report with no control, no replication, and no data on long-term outcomes beyond the described remission. The patient’s poor compliance with oral medications was overcome by intravenous infliximab, but this does not constitute evidence that infliximab is effective for CdLS itself. What is missing is any controlled trial, any systematic collection of treatment outcomes in CdLS patients with gastrointestinal complications, and any understanding of whether the ulcerative colitis in this patient was related to his CdLS or coincidental. No funding for such trials is mentioned, no patient stratification by genetic subtype is attempted, and no prospective study design is described.
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 Crohn s and Colitis · 2013 · 2 citations
Cornelia de Lange syndrome in association with ulcerative colitis: A case report
AbstractDear Sir, Cornelia de Lange syndrome (CdLS) is a rare multi-system genetic disorder with an incidence rate between 1:10 000 and 1:50 000. It is characterized by growth and developmental delay, distinctive facial dysmorphism, limb malformations and multiple organ defects.1 Patients with CdLS usually also have behavioral problems. CdLS has been found associated with mutations in the NIPBL, SMC1A, and SMC3 genes.2 A variety of gastrointestinal abnormalities have been described, including malrotation, colonic duplication and non-fixation of the colon. A high mortality rate caused by cecal volvulus in CdLS patients has also been reported.3,4 There are several reports of association of ulcerative colitis with rare genetic syndromes. However, no case of coexistence of CdLS with ulcerative colitis has been reported so far. We report a 20-year-old male with CdLS that was diagnosed with ulcerative colitis. He was admitted to the hospital with a two month history of bloody diarrhea (about 10 bowel movements per day), abdominal pain and weight loss of 6 kg. He was diagnosed since childhood with CdLS mainly based on the clinical findings. He had a positive family history (mother) with ulcerative colitis. Physical examination revealed facial dysmorphism (Fig. 1) as well as significant growth and mental retardation. The laboratory tests revealed mild anemia (hemoglobin 12.5 g/dL, hematocrit 37.3%) and elevated ESR (80 mm/h) and CRP (12.5 mg/dL) with normal liver and kidney functions. The patient underwent colonoscopy that showed all the parts of the colon having multiple ulcers, marked erythema and friability (endoscopic partial Mayo score 3). Histology showed loss of goblet cells, crypt abscesses and chronic inflammation in the lamina propria findings consisted with the diagnosis of ulcerative colitis. Initial treatment of the patient was mesalazine 3 gr/d per os and enema 4 gr/d as well as prednizolone 30 mg per os but without any response mainly due to the behavioral problems and the poor compliance of the patient to the treatment. Even if his parents were giving him the medications he was trying to avoid them by voluntary emesis. Afterwards infliximab 5 mg/kg (loading dose at 0, 2 and 6 weeks) was administered and the patient showed prompt clinical response. Currently, the patient is in clinical remission under treatment with infliximab 5 mg/kg every 8 weeks. The presented case represents a rare coexistence of CdLS with ulcerative colitis that has not been previously reported in the literature. An interesting point also is the problems with the treatment in this situation which were overcome by the IV administration of infliximab. The pathophysiology of the association between CdLS and ulcerative colitis remains unknown but the positive family history of this patient could play also a prominent role. All authors do not have any conflict of interest regarding this report. Characteristic facial dysmorphism of the patient. Characteristic facial dysmorphism of the patient.
International journal of pediatrics · 2016 · 0 citations
Progress in cornelia de lange syndrome
AbstractCornelia de Lange syndrome is a rare congenital disease, which was firstly reported on 1933.It usually causes multiple organs dysplasia.Clinical manifestations include severe growth retardation, cognitive impairment, characteristic facial and upper limb defects.With the rapid development of medical science, especially in genetics and molecular biology, much research on the pathogenesis of Cornelia De Lange syndrome has been performed.Herein, we review the progress in this rare disease in recent years.
Key words:
Cornelia de Lange syndrome; Pathogenesis
Ultrasound in Obstetrics and Gynecology · 2014 · 0 citations · open access
<scp>OP</scp>27.06: Cornelia de Lange syndrome: new features for prenatal diagnosis
AbstractThe Cornelia de Lange syndrome is a genetic disorder characterized by multiple development anomalies. Three mutations are known (NIPBL, SMC1A and SMC3) but the majority of cases is related to de novo mutations. Supporting information can be found in the online version of this abstract Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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.
