DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for megalocornea — 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 moduleMegalocornea 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 megalocornea 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
nuclear factor I X (NFIX) — NFIX 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 9WA7 · 2.31 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
X-linked megalocornea is a congenital condition in which affected males have corneal diameters between 13.0 and 16.5 mm, based on five families studied in 1991. In that same report, arcus juvenilis, mosaic corneal dystrophy, and cataracts were found only in adult affected males, and no carrier female abnormality was identified. The gene locus was mapped to Xq12-q26, near the locus for Aarskog syndrome.
In 2013, a family with a woman and her four sons aged 3 to 15 years was examined. Three sons had horizontal corneal diameters of 14 mm; the mother and the fourth son had normal diameters of 12 mm. Central corneal thickness in the affected sons averaged 474 microns, compared with 604 microns in the unaffected brother. Corneal topographic imaging gave an average K value of 44.4 D in affected individuals versus 41.6 D in the unaffected sibling. A novel hemizygous frameshift mutation in the CHRDL1 gene, c.167delC (p.(Pro56Leu*8)), was found in the affected sons and in the heterozygous state in their mother; it was absent in the unaffected brother and in unrelated controls. This provided the initial confirmation that X-linked megalocornea is associated with CHRDL1 mutations.
A 2015 study of two probands from independent families in southern Italy, plus three other affected family members, identified an 11-base pair deletion leading to a stop codon in the second coding exon of CHRDL1. The mutation was not detected in 11 unaffected family members. The authors noted that detecting CHRDL1 mutations is useful for differential diagnosis among different forms of megalocornea.
No treatment or intervention is described in any of these reports. The natural history of the condition — particularly the risk and timing of cataract formation, and whether corneal thickness or curvature changes with age — remains incompletely characterised. Larger, prospective studies with standardised measurements across multiple pedigrees are missing, as are any trials of surgical or medical management.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Ophthalmology · 1991 · 65 citations
Description of X-Linked Megalocornea With Identification of the Gene Locus
AbstractWe studied the clinical appearance and inheritance in five families with X-linked megalocornea. Affected male subjects had corneal diameters between 13.0 and 16.5 mm. Arcus juvenilis, mosaic corneal dystrophy, and cataracts were found only in adult affected male subjects. No carrier female abnormality was identified. The gene locus for the X-linked form is in the region Xq12-q26. This is near the locus described for Aarskog (facial-digital-genital) syndrome, Xq12-13.
X-linked Megalocornea Associated with the Novel<i>CHRDL1</i>Gene Mutation p.(Pro56Leu*8)
AbstractBACKGROUND: The genetic basis of X-linked megalocornea (MGC1) was reported in 2012 to be caused by mutations in the CHRDL1 gene. We sought to confirm that mutations in CHRDL1 are associated with MGC1 in a previously unreported pedigree. MATERIALS AND METHODS: Slit lamp examination, corneal pachymetry, corneal topography and DNA collection for screening of the CHRDL1 gene were performed for members of an affected family. RESULTS: Examination of a woman and her four sons, ranging in age between 3 and 15 years, demonstrated horizontal corneal diameters of 14 mm in three of the four sons and a normal corneal diameter of 12 mm in the mother and other son. Central corneal thickness in the individuals with enlarged corneal diameters averaged 474 microns, compared to 604 microns in their unaffected brother. Corneal topographic imaging demonstrated an average K value of 44.4 D in the affected individuals compared with 41.6 D in their unaffected sibling. Screening of the CHRDL1 gene demonstrated the novel hemizygous frameshift mutation c.167delC (p.(Pro56Leu*8)) in exon 3 in the affected individuals and in the heterozygous state in their mother. This mutation was not present in the unaffected brother or in unrelated controls. CONCLUSION: We provide the initial confirmation that X-linked megalocornea is associated with mutations in the CHRDL1 gene.
Novel Mutation in the CHRDL1 Gene Detected in Patients With Megalocornea
AbstractPURPOSE: The aim of this study was to determine the mutation associated with X-linked megalocornea (MGC1) found in 2 patients from the same area in southern Italy. METHODS: Diagnosis of megalocornea was confirmed by detailed ophthalmic examination in 2 probands from independent families and in another 3 affected family members. Genomic DNA of the probands was used to amplify and sequence all the coding regions of CHRDL1. RESULTS: Megalocornea diagnosis was associated with a novel mutation found in the probands and affected kindreds (5 subjects). The mutation is an 11-base pair deletion that leads to a stop codon in the second coding exon of the CHRDL1 gene. Research on the CHRDL1 mutation was also performed on other family members (11 subjects) not affected by MGC1, and the mutation was not detected in unaffected male family members. CONCLUSIONS: The detection of mutations in the CHRDL1 gene is useful for differential diagnosis with different forms of megalocornea.
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.
