DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for coloboma — screening already-approved drugs against its 29-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleColoboma maps to a 29-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 coloboma 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
Rho GTPase activating protein 35 (ARHGAP35) — ARHGAP35 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3C5H · 1.8 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2018 study, laser-assisted microdissection and microarray analysis of mouse optic cup tissues showed that the optic fissure region has a unique transcriptome. Morpholino knockdown of one newly identified optic-fissure-specific gene, afap1l2, in zebrafish disrupted optic fissure closure by regulating pax2a expression. The authors state this provides a foundation for exploring human coloboma aetiology, but no human data or therapeutic intervention was tested.
A 2025 paper describes a novel transgenic mouse line, Retinal and Iris Coloboma (RICO), created by inserting a human VEGF-165 gene under a neuron-specific enolase promoter. These mice are viable as homozygotes and show fully penetrant autosomal semidominant coloboma. The coloboma is linked to a transgene-induced genomic rearrangement on chromosome 13 that drives aberrant hVEGF expression and persistence of periocular mesenchyme in the optic fissure. RNA sequencing revealed changes in multiple coloboma-associated genes, and deletions of the human homologous locus were found in coloboma patients. This is a model for studying pathogenesis, not a treatment.
A 2006 case report describes a five-month-old girl with isolated bilateral upper lid coloboma involving two-thirds of each lid and symblepharon, with no other congenital anomalies. Surgical repair used a lower-lid switch flap in two stages, with flap separation after two weeks. The patient was discharged five days after the second surgery, and the authors report a good functional and cosmetic result. This is a surgical repair, not a drug intervention.
A 2024 review notes that recent progress in ocular coloboma has focused on identifying genetic mutations and molecular pathways, improving understanding of normal eye development and disease origins. However, it states plainly that a significant portion of isolated ocular coloboma cases still lack a definitive genetic or environmental explanation. No drug, treatment, or clinical trial for coloboma is described in any of these abstracts. What remains missing is a clear genetic or environmental cause for most isolated cases, any clinical trial testing a pharmacological intervention, and patient stratification that might identify subgroups responsive to a specific molecular therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Regional Gene Expression Profile Comparison Reveals the Unique Transcriptome of the Optic Fissure
AbstractPurpose: The optic fissure (OF) is a transient opening in the ventral optic cup (OC) that acts as a passage for blood vessels and retinal ganglion cell axons during early eye development. Failure to close the OF is the developmental basis for uveal coloboma, a congenital blinding eye disease that significantly contributes to childhood blindness. Genes specifically expressed in the OF region may play important roles in OF development and function. The aim of this study was to characterize the transcriptome of OC cells in the OF region and investigate the function of OF-specific genes during OF closure. Methods: Laser-assisted microdissection was used to collect different regions of OC tissues. Microarray analysis was used to obtain and compare gene expression profiles of different OC regions. RNA in situ hybridization (ISH) was used to further characterize OF-specific gene expression patterns. Morpholino knockdown in zebrafish was used to study the function of a newly discovered OF-specific gene during OF closure. Results: Microarray comparison revealed that the OC at the OF region exhibited a unique gene expression profile. OC expression patterns of a number of newly discovered OF-specific genes were confirmed by ISH. Morpholino knockdown and downstream target expression and function analysis demonstrated that afap1l2, a newly discovered OF-specific gene, controls OF closure by regulating pax2a expression. Conclusions: Our study characterized the unique transcriptome of the OF region of the OC and demonstrated the essential role of a newly discovered OF-specific gene in OF closure. This study provides a valuable foundation for future mechanism dissection in OF development and physiology, and for human coloboma etiology exploration.
Nigerian Journal of Medicine · 2006 · 4 citations · open access
Isolated bileteral upper lid coloboma a case report
AbstractBACKGROUND: Congenital upper lid colobomas may be associated with ocular and systemic anomalies. This paper reports an isolated bilateral upper lid coloboma. METHOD: A report of a case of bilateral upper lid coloboma with discussion of relevant literature. RESULTS: A 5-month old healthy baby girl presented with isolated bilateral upper lid coloboma. The coloboma was as large as two thirds of each upper lid with symblepharon. She had no other associated congenital anomalies reported by various workers. The upper lid defect in each eye was repaired in two stages. She had a flap from the lower lid using the lid switch technique and flap separation 2 weeks after the first surgery, in a combined surgery by a plastic surgeon and ophthalmologists. A good functional and cosmetic result was achieved from the treatment. The patient was discharged five days after the second surgery. CONCLUSION: This case shows that lid coloboma could be an isolated problem in a child. Early and appropriate surgical intervention is necessary for good visual and functional outcome.
Transgene-Induced Chromosomal Rearrangement With Aberrant Human Vascular Endothelial Growth Factor at the Optic Fissure Leads to Uveal Coloboma in Mice
AbstractPurpose: The pathogenesis of uveal coloboma, a potentially blinding congenital ocular malformation, is incompletely understood. We characterize a novel mouse model of coloboma, Retinal and Iris Coloboma (RICO). Methods: Transgenic mice were created by insertion of a human vascular endothelial growth factor-165 (hVEGF) gene driven by a neuron-specific enolase promoter. Mice were examined clinically and histologically, and the insertion site was characterized by fluorescence in situ hybridization and genomic sequencing. Gene expression changes were assessed with RNA sequencing, immunofluorescence, and in situ hybridization. Results: RICO mice are viable in the homozygous state and exhibit fully penetrant autosomal semidominant coloboma. Coloboma is associated with persistence of periocular mesenchyme in the optic fissure, likely contingent on a specific, transgene insertion-induced genomic rearrangement on chromosome 13 that drives aberrant hVEGF expression. RICO eye cups exhibit altered expression of genes in the vicinity of the insertion site, where deletions of the human homologous locus were found in coloboma patients. RNA sequencing demonstrates changes in multiple coloboma-associated genes. Conclusions: RICO represents a useful model for studying the pathogenesis of human coloboma.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
IMPROVEMENT OF SURGICAL TACTICS AND TREATMENT OF COMBINED INJURIES IN CHILDREN
AbstractOcular coloboma defects are a frequent source of eye-related issues in children and can lead to notable vision problems. Recent progress in this field has mainly focused on pinpointing numerous genetic mutations associated with the condition and uncovering various molecular pathways. This has not only enhanced our knowledge of the origins of ocular coloboma but has also deepened our understanding of normal eye development. Despite these advancements, a significant portion of isolated ocular coloboma cases still lack a definitive genetic or environmental explanation.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
IMPROVEMENT OF SURGICAL TACTICS AND TREATMENT OF COMBINED INJURIES IN CHILDREN
AbstractOcular coloboma defects are a frequent source of eye-related issues in children and can lead to notable vision problems. Recent progress in this field has mainly focused on pinpointing numerous genetic mutations associated with the condition and uncovering various molecular pathways. This has not only enhanced our knowledge of the origins of ocular coloboma but has also deepened our understanding of normal eye development. Despite these advancements, a significant portion of isolated ocular coloboma cases still lack a definitive genetic or environmental explanation.
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.
