DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Cornelia de Lange syndrome — screening already-approved drugs against its 13-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 maps to a 13-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 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
inositol monophosphatase 1 (IMPA1) — IMPA1 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 4-oxidanylphenoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6GIU · 1.39 Å · ligand [1-(4-oxidanylphenoxy)-1-phosphono-ethyl]phosphonic acid (L69). Experimental structure, not a prediction.
What the evidence adds up to
Cornelia de Lange syndrome is a rare multi-system genetic disorder with an incidence reported between 1:10,000 and 1:50,000 live births, and has been considered due to a new dominant mutation. Main clinical features include growth retardation, developmental delay, hirsutism, structural limb abnormalities, mental retardation, and facial growth discrepancies. Main causes of death include pneumonia along with cardiac, respiratory and gastrointestinal abnormalities. Mutations in the NIPBL, SMC1A, and SMC3 genes have been found associated with CdLS, and the syndrome remains the prototype for the cohesinopathy disorders. A variety of gastrointestinal abnormalities have been described, including malrotation, colonic duplication and non-fixation of the colon, and a high mortality rate caused by cecal volvulus has been reported.
A 2013 case report describes a 20-year-old male with CdLS diagnosed with ulcerative colitis, a coexistence not previously reported. He presented with bloody diarrhea, abdominal pain, and weight loss. Initial treatment with mesalazine 3 g/d orally and enema 4 g/d plus prednisolone 30 mg orally produced no response, mainly due to behavioural problems and poor compliance; the patient attempted to avoid oral medications by voluntary emesis. Infliximab 5 mg/kg was then administered intravenously as a loading dose at 0, 2, and 6 weeks, and the patient showed prompt clinical response. At the time of reporting, the patient was in clinical remission under treatment with infliximab 5 mg/kg every 8 weeks. The pathophysiology of the association between CdLS and ulcerative colitis remains unknown, and the positive family history of this patient could play a role.
No controlled trials of any drug for the core features of Cornelia de Lange syndrome are reported in these abstracts. The only treatment described is for a coincident ulcerative colitis in a single patient, and that treatment was given intravenously to overcome behavioural non-compliance. What is still missing is any clinical trial designed to test a drug against the fundamental developmental and cognitive impairments of CdLS, along with the funding and patient stratification needed to conduct such a trial in a rare disease.
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 Indian Society of Pedodontics and Preventive Dentistry · 2005 · 17 citations · open access
Cornelia de-Lange syndrome
AbstractCornelia De Lange syndrome is a relatively uncommon, multiple congenital anomaly / mental retardation disorder of unknown etiology. Its incidence has been reported to vary from 1 : 30,000 to 1 : 50,000 of live births, without any known racial predilection. However, it has been considered to be due to a new dominant mutation. Main clinical features of this syndrome include growth retardation, developmental delay, hirsutism, structural limb abnormalities, mental retardation and facial growth discrepancies. Main causes of death in such patients include pneumonia along with cardiac, respiratory and GI abnormalities.
Cornelia de Lange syndrome in a mother and daughter
AbstractThe Cornelia de Lange syndrome was first described in 1933. Since then, more than 250 cases have been described in the medical literature. It has generally been considered to be sporadic, but several authors have raised the possibility of genetic factors. We present a mother and child affected with Cornelia de Lange syndrome and raise the possibility of autosomal dominant inheritance.
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.
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.
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
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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