DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Coffin-Siris syndrome 8 — 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 moduleCoffin-Siris syndrome 8 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 coffin-siris syndrome 8 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
SWI/SNF related BAF chromatin remodeling complex subunit C2 (SMARCC2) — SMARCC2 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…
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RCSB Protein Data Bank · entry 7VDV · 3.4 Å · ligand BERYLLIUM TRIFLUORIDE ION (BEF). Experimental structure, not a prediction.
What the evidence adds up to
The two 2023 case reports describe four patients in total, all with confirmed mutations in either ARID1A or SMARCB1. The 2022 paper reports two ARID1A cases with dissimilar presentation and clinical course. The 2016 paper describes a single child with the classic features of developmental delay, seizures, coarse facial features, body hypertrichosis, scalp hypotrichosis, and sensorineural hearing loss. No drug treatment is mentioned in any of these abstracts.
The 2023 prenatal report widens the known phenotypic spectrum by documenting severely hypoplastic right ventricle with ventricular septal defect, truncus arteriosus type III, persistent left superior and inferior caval vein, bilateral olfactory nerve aplasia, and hypoplastic thymus in two fetuses. One fetus carried a SMARCB1 deletion (c.1066_1067del) and the other a novel ARID1A splice-site deletion (c.1920+3_1920+6del). These findings confirm that Coffin-Siris syndrome can present with life-threatening structural heart and brain anomalies detectable before birth.
All abstracts emphasise that Coffin-Siris syndrome is clinically heterogeneous, with no consistent genotype-phenotype correlation reported across these small series. The 2022 paper explicitly states that the two ARID1A cases had dissimilar presentations. No quantitative survival data, response rates, or sample sizes beyond single cases or pairs are provided. No therapeutic intervention is tested or proposed.
What is missing is any clinical trial, any drug tested in these patients, any biomarker for severity, and any systematic natural history study that could power a future trial. The field lacks patient registries large enough to stratify by the 12 known causative genes, and no funding for such registries is mentioned.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Case Reports · 2022 · 5 citations · open access
<scp>Coffin–Siris</scp> syndrome: Clinical description of two cases
AbstractCoffin-Siris syndrome is a rare disorder, which can be difficult to recognize. A broad spectrum of nonspecific clinical features is associated with Coffin-Siris syndrome, and the expression of these features is diverse. We describe two cases with Coffin-Siris syndrome with mutations in the ARID1A gene, with dissimilar presentation and clinical course.
Sage Journals Data · 2023 · 0 citations · open access
Prenatal Coffin-Siris Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Disease
AbstractCoffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically have variable degree of developmental delay or intellectual disability, muscular hypotonia, dysmorphic facial features, sparse scalp hair, but otherwise hirsutism and fifth digit nail or distal phalanx hypoplasia or aplasia. Coffin-Siris syndrome is caused by pathogenic variants in 12 different genes including <i>SMARCB1</i> and <i>ARID1A</i>. Pathogenic <i>SMARCB1</i> gene variants cause Coffin-Siris syndrome 3 whereas pathogenic <i>ARID1A</i> gene variants cause Coffin-Siris syndrome 2. Here, we present two prenatal Coffin-Siris syndrome cases with autosomal dominant pathogenic variants: <i>SMARCB1</i> gene c.1066_1067del, p.(Leu356AspfsTer4) variant, and a novel <i>ARID1A</i> gene c.1920+3_1920+6del variant. The prenatal phenotype in Coffin-Siris syndrome has been rarely described. This article widens the phenotypic spectrum of prenatal Coffin-Siris syndrome with severely hypoplastic right ventricle with VSD and truncus arteriosus type III, persisting left superior and inferior caval vein, bilateral olfactory nerve aplasia, and hypoplastic thymus. A detailed clinical description of the patients with ultrasound, MRI, and <i>post mortem</i> pictures of the affected fetuses showing the wide phenotypic spectrum of the disease is presented.
International Journal of Contemporary Pediatrics · 2016 · 0 citations · open access
Coffin siris syndrome: a rare clinical entity
AbstractCoffin-siris syndrome (CSS) is a rare, clinically heterogeneous disorder considered in the setting of prenatal onset of mild to moderate growth deficiency, facial dysmorphism, cognitive/developmental delay, and speech impairment, moderate to severe hypotonia, seizures and 5 th finger/nail hypoplasia. The child had distinctive features of CSS like developmental delay, seizures, and coarse facial features, body hypertrichosis, scalp hypotrichosis and SNHL.
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.
