DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Weill-Marchesani syndrome — 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 moduleWeill-Marchesani syndrome 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 weill-marchesani 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
fibrillin 1 (FBN1) — FBN1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1UZK · 1.35 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Weill-Marchesani syndrome is a rare connective tissue disorder. Three siblings with typical manifestations showed spherophakia, severe myopia, a shallow anterior chamber, and narrow angle glaucoma; two underwent laser iridotomy and drug treatment, and the third had a lens removed after injury and examined by microscopy. An 11-year-old male patient’s anaesthetic management was reported. A family case described four of eight children affected by spherophakia, brachymorphy and brachydactyly. Twin sisters of 18 months presented with microspherophakia, ectopia lentis, lenticular myopia, depressed nasal bridge, broad square head, stubby spade-like hands, and thick skin. A 75-year-old female with morphometric features of Weill-Marchesani syndrome had bilateral Morgagni hernia, an association reported for the first time.
A homozygous missense mutation, c.41T>A, in the ADAMTS10 gene was identified in a 19-year-old female with proportionate short stature, brachydactyly, joint stiffness, and microspherophakia. In silico analysis gave conflicting results on the mutation’s effects on protein function, but it was predicted to affect the leader sequence. Molecular characterisation in HEK293 Ebna cells showed intracellular mis-targeting of the ADAMTS10 protein with reduced concentration in the endoplasmic reticulum, a large reduction in glycosylation of the cytoplasmic fraction of the mutant protein versus wild-type, and a lack of secretion of the mutant protein.
No drug treatment for the syndrome itself is described in these abstracts. The only drug mention is “drug treatment” for glaucoma in the 1990 sibling series, with no agent named. No clinical trial, no quantitative outcome data for any systemic therapy, and no survival or response rates appear. What is missing is any trial of a drug intended to modify the underlying connective tissue or lens pathology, any patient stratification by genotype, and any funding for such a 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.
British Journal of Ophthalmology · 1990 · 21 citations · open access
Histology of the lens in the Weill-Marchesani syndrome.
AbstractThe Weill-Marchesani syndrome is a rare systemic connective tissue disease characterised by small stature, brachydactyly, ectopia lentis, and spherophakia. Three siblings with typical manifestations of this syndrome were reported. The ophthalmological findings in all these cases were spherophakia, severe myopia, a shallow anterior chamber, and narrow angle glaucoma. Two cases underwent laser iridotomy and drug treatment. In the third case the lens was removed from the eye because of injury, and this lens was examined by light and electron microscopy.
Anesthetic management of a patient with Weill–Marchesani syndrome
AbstractWeill-Marchesani syndrome is characterized by short stature, brachydactylyl, myopia, microspherophakia, lens dislocation, glaucoma, joint stiffness, restricted articular movements and facial features. The anesthetic management of an 11-year-old-male patient with diagnosis of this syndrome is reported.
Archivos de la Sociedad Española de Oftalmología · 2006 · 3 citations · open access
Síndrome de Weill-Marchesani: afectación familiar
AbstractCASE REPORT: We report the case of a child short in stature with brachydactyly and brachymorphy who was referred to our office complaining of poor vision. This was a case of Weill-Marchesani's syndrome described in a family, in which four of the eight children were affected by spherophakia, brachymorphy and brachydactyly. DISCUSSION: There are few familial cases of Weill-Marchesani's syndrome reported in the literature. Both autosomal dominant and recessive inheritances have been described. The opththalmologist plays a crucial role in its diagnosis and management, since the ocular involvement is the most severe one.
Zurich Open Repository and Archive (University of Zurich) · 2015 · 0 citations · open access
Identification and molecular characterisation of a homozygous missense mutation in the ADAMTS10 gene in a patient with Weill-Marchesani syndrome
AbstractWeill-Marchesani syndrome is a rare disorder of the connective tissue. Functional variants in ADAMTS10 are associated with Weill-Marchesani syndrome-1. We identified a homozygous missense mutation, c.41T>A, of the ADAMTS10 gene in a 19-year-old female with typical symptoms of WMS1: proportionate short stature, brachydactyly, joint stiffness, and microspherophakia. The ADAMTS10 missense mutation was analysed in silico, with conflicting results as to its effects on protein function, but it was predicted to affect the leader sequence. Molecular characterisation in HEK293 Ebna cells revealed an intracellular mis-targeting of the ADAMTS10 protein with a reduced concentration of the polypeptide in the endoplasmic reticulum. A large reduction in glycosylation of the cytoplasmic fraction of the mutant ADAMTS10 protein versus the wild-type protein and a lack of secretion of the mutant protein are also evident in our results.In conclusion, we identified a novel missense mutation of the ADAMTS10 gene and confirmed the functional consequences suggested by the in silico analysis by conducting molecular studies.
Weill–Marchesani Syndrome in 18-Month-Old Twin Sisters
AbstractWeill–Marchesani syndrome is a rare genetic disorder recognized by characteristic ocular and connective tissue abnormalities. This case report demonstrates this disorder in twin sisters with microspherophakia, ectopia lentis, and lenticular myopia. In addition to ocular findings, the systemic associations included depressed nasal bridge with a broad and square head, stubby spade-like hands, and thick skin.
International Journal of Research in Medical Sciences · 2017 · 0 citations · open access
Bilateral morgagni hernia in a case of Weill-Marchesani syndrome-a rare association
AbstractMorgagni hernia constitutes only about 2% of all diaphragmatic hernias and bilateral Morgagni hernia is extremely rare. Here we present a 75 year old female patient with morphometric features of Weill-Marchesani syndrome who has bilateral Morgagni hernia. This association is reported for the first time in literature.
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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