DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Jackson-Weiss syndrome — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleJackson-Weiss syndrome maps to a 3-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 jackson-weiss 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
fibroblast growth factor receptor 2 (FGFR2) — FGFR2 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 acpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6V6Q · 2.46 Å · ligand PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER (ACP). Experimental structure, not a prediction.
What the evidence adds up to
Jackson-Weiss syndrome is an autosomal dominant condition with high penetrance and variable expressivity, defined by craniosynostosis and characteristic radiographic anomalies of the feet. A 2001 study identified a previously unrecognised branch of the original family in which the syndrome was first described. Affected members carried an Ala344Gly substitution in fibroblast growth factor receptor 2, the only mutation documented in a family meeting the clinical diagnosis of Jackson-Weiss syndrome. The proband in that branch showed a novel phenotype including leg-length discrepancy and unilateral absence of the fifth digital ray in her right foot, illustrating the wide variability of expression.
A 2000 report described a patient with skeletal findings of Jackson-Weiss syndrome but only mild craniofacial anomalies. Molecular analysis revealed a heterozygous P252R missense mutation in FGFR1, previously reported only with Pfeiffer syndrome-like manifestations. The authors noted that mutations in the immunoglobulin-like II-III linker region of FGFR1 and FGFR3 may present as a skeletal dysplasia affecting the appendicular skeleton, including brachydactyly, short broad middle phalanges, phalangeal epiphyseal coning, and broad halluces. This was presented as a further example of an activated FGFR molecule producing overlapping manifestations across FGFR syndromes.
A 1994 study of a large South Australian kindred described radiological findings not previously reported in Jackson-Weiss syndrome: coned epiphyses, distal and middle phalangeal hypoplasia, and carpal bone malsegmentation in the hands; and in the feet, coned epiphyses, hallux valgus, phalangeal, tarso-navicular and calcaneonavicular fusions, and uniform absence of metatarsal fusions. Linkage analysis excluded allelism with Saethre-Chotzen syndrome at 7p21 and with a cephalosyndactyly syndrome mapping to 5qter.
No clinical trial data exist for any drug in Jackson-Weiss syndrome. The literature consists entirely of case reports and kindred descriptions. What is missing is any systematic effort to stratify patients by specific FGFR mutation, any preclinical model suitable for drug testing, and any funding for a natural history study that could define endpoints for a future trial.
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 · 2000 · 62 citations
Clinical findings in a patient withFGFR1 P252R mutation and comparison with the literature
AbstractWe report on a patient with the skeletal findings of Jackson-Weiss syndrome, who manifests only mild craniofacial anomalies. Molecular analysis of her fibroblast growth factor receptor 1 gene (FGFR1) identified a heterozygous P252R missense mutation, previously only reported with FGFR1-Pfeiffer syndrome like manifestations. Mutations in the immunoglobulin-like, II-III (IgII-III) linker region of FGFR1 and FGFR3 molecules may present as a skeletal dysplasia affecting the appendicular skeleton including, brachydactyly, short broad middle phalanges, phalangeal epiphyseal coning and broad halluces. This communication is a further example of the phenomenon of an activated FGFR molecule resulting in overlapping manifestations in FGFR syndromes.
American Journal of Medical Genetics · 1994 · 26 citations
Jackson‐Weiss syndrome: Clinical and radiological findings in a large kindred and exclusion of the gene from 7p21 and 5qter
AbstractWe describe the clinical and radiological manifestations of the Jackson-Weiss syndrome (JWS) in a large South Australian kindred. Radiological abnormalities not previously described in the hands include coned epiphyses, distal and middle phalangeal hypoplasia, and carpal bone malsegmentation. New radiological findings in the feet include coned epiphyses, hallux valgus, phalangeal, tarso-navicular and calcaneonavicular fusions, and uniform absence of metatarsal fusions. Absence of linkage to eight markers along the short arm of chromosome 7 excluded allelism between JWS and Saethre-Chotzen syndrome at 7p21. No linkage was detected to D5S211, excluding allelism to another recently described cephalosyndactyly syndrome mapping to 5qter.
American Journal of Medical Genetics · 2001 · 22 citations
Century of Jackson-Weiss syndrome: Further definition of clinical and radiographic findings in ?lost? descendants of the original kindred
AbstractJackson-Weiss syndrome (JWS) is a condition consisting of craniosynostosis characterized by premature fusion of the cranial sutures and/or characteristic radiographic anomalies of the feet. The condition is inherited as an autosomal dominant trait with high penetrance and variable expressivity. Six different mutations in the fibroblast growth factor receptor 2 have been identified in patients with the clinical diagnosis of JWS. Jabs et al. [1994: Nat Genet 8:275-279] identified an Ala344Gly substitution in two branches of the family in which the clinical syndrome was originally described. This is the only publication to document this mutation in a family with the clinical diagnosis of JWS. In this study, we have identified a previously unrecognized branch of the original family with individuals that meet the clinical criteria for the diagnosis of JWS. We demonstrate that a mutation that produces the Ala344Gly substitution is present in affected members. This family illustrates the widely variable expression of the mutation, including a novel phenotype in the proband with a leg-length discrepancy and unilateral absence of the fifth digital ray in her right foot. We identify the clinical and detailed radiographic features of each affected individual and offer considerations when making the diagnosis of JWS.
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.
