DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Nager acrofacial dysostosis — 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 moduleNager acrofacial dysostosis 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 nager acrofacial dysostosis 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
splicing factor 3b subunit 4 (SF3B4) — SF3B4 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 2~{s},3~{s},4~{e},6~{s},7~{r},10~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7EVO · 2.5 Å · ligand [(2~{S},3~{S},4~{E},6~{S},7~{R},10~{R})-3,7-dimethyl-2-[(2~{E},4~{E},6~{R})-6-methyl-6-oxidanyl-7-[(2~{R},3~{R})-3-[(2~{R},3~{S})-3-oxidanylpentan-2-yl]oxiran-2-yl]hepta-2,4-dien-2-yl]-7,10-bis(oxidanyl)-12-oxidanylidene-1-oxacyclododec-4-en-6-yl] 4-cycloheptylpiperazine-1-carboxylate (9B0). Experimental structure, not a prediction.
What the evidence adds up to
Nager acrofacial dysostosis is defined by malar, mandibular, and maxillary hypoplasia, macrostomia, abnormal ears, and radial defects; lower limbs are usually normal. Four patients reported in 1983 extended the characterisation to include lower limb defects and discussed differential diagnoses such as postaxial defect syndrome, Fontaine syndrome, distal 2q duplication syndrome, and hemifacial microsomia with radial defect. A 1988 report described a patient with limb findings of intermediate severity who also had hydrocephalus, micropolygyria, and tetralogy of Fallot, suggesting either heterogeneity or a single condition with widely variable expression.
A 2016 review of nine patients (six male, three female) from two craniofacial units found a mean age at presentation of 3.7 years (range 8 days to 11.8 years) and mean follow-up of 2.2 years (2 months to 19 years). SF3B4 mutation was noted in two patients; one patient had an X:9 translocation. Seven patients (77.8%) had obstructive sleep apnoea, with five diagnosed as severe. Craniofacial surgery included mandibular advancement in five patients, temporo-mandibular joint reconstruction in two, and genioplasty in one. Upper limb procedures included pollicization of the index in four patients, excision of extra radial digits in two, and thumb duplication correction in one.
The condition is commonly mistaken for Treacher Collins syndrome, which shares the same craniofacial phenotype but lacks hand anomalies. The 2016 review advocates early pollicization for thumb anomalies to prevent impairment in manual dexterity, but this is a surgical management recommendation, not a drug therapy. No pharmacological treatments are described in any of the abstracts.
What is still missing is any drug or molecular therapy for Nager syndrome. No trials of medical treatments exist in these reports. The genetic basis (SF3B4 mutation) is identified in only a minority of patients, and the variable expression means patient stratification for any future trial would be difficult. Funding for natural history studies and for developing animal models that could test small molecules or gene-based approaches has not been reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics · 1983 · 77 citations
Differential diagnosis of Nager acrofacial dysostosis syndrome: Report of four patients with Nager syndrome and discussion of other related syndromes
AbstractAbstract We report four patients with Nager acrofacial dysostosis (AFD) syndrome and review all previous cases. This leads to an extended characterization of the Nager syndrome—eg, description of lower limb defects—and also to a discussion of the differential diagnosis which includes AFD postaxial defect syndrome, Fontaine syndrome, distal 2q duplication syndrome, hemifacial microsomia/Goldenhar radial defect syndrome, and some others.
American Journal of Medical Genetics · 1988 · 28 citations
Nager acrofacial dysostosis: Evidence for apparent heterogeneity
AbstractNager acrofacial dysostosis is characterized by malar, mandibular, and maxillary hypoplasia, macrostomia, abnormal ears, and radial defects. The lower limbs are usually normal. Two patients were reported with many of these manifestations, in addition to severe facial clefts and limb deficiency. These more severely affected patients were thought to have a severe form of Nager acrofacial dysostosis or a new syndrome. We report on a patient with limb findings of intermediate severity. This patient also had hydrocephalus, micropolygyria, and tetralogy of Fallot. This may indicate apparent heterogeneity or a single condition with widely variable expression.
Journal of Craniofacial Surgery · 2016 · 19 citations
The Craniofacial and Upper Limb Management of Nager Syndrome
AbstractINTRODUCTION: Nager syndrome is a rare condition characterized by craniofacial and upper limb abnormalities. It is commonly mistaken for Treacher Collins syndrome, with which it shares the same craniofacial phenotype. However, patients with Treacher Collins do not exhibit hand anomalies, which are seen in patients with Nager syndrome. This paper reviews the multidisciplinary management of patients with Nager syndrome who were treated at the Australian Craniofacial Unit, Adelaide and the Erasmus Medical Centre, Rotterdam. METHODS: The database of both units was scrutinized and the case-notes of the patients with Nager syndrome were reviewed. Data was collected on patient demographics, surgical management, complications, and outcome. RESULTS: Nine patients (6 M:3 F) were identified with Nager syndrome, with a mean age at presentation of 3.7 years (range 8 days to 11.8 years). The mean follow-up time was 2.2 years (2 months to 19 years). SF3B4 mutation was noted in 2 patients and 1 patient had an X:9 translocation. Seven (77.8%) had obstructive sleep apnoea, with 5 patients diagnosed as severe obstructive sleep apnoea. Four patients had pollicization of their index, 2 patients had excision of extra radial digits and 1 patient underwent thumb duplication correction. Craniofacial surgery included mandibular advancement in 5 patients, temporo-mandibular joint reconstruction in 2 patients, and a genioplasty in 1 patient. CONCLUSION: Nager syndrome is a rare acrofacial dysostosis syndrome that is best managed within the realms of a multidisciplinary team. The authors would advocate early pollicization in patients with thumb anomalies to prevent any impairment in manual dexterity.
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.
