DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for coloboma of optic nerve — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleColoboma of optic nerve maps to a 6-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 of optic nerve 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
serpin family C member 1 (SERPINC1) — SERPINC1 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 z9ldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3KCG · 1.7 Å · ligand methyl 2,3,6-tri-O-sulfo-alpha-D-glucopyranoside (Z9L). Experimental structure, not a prediction.
What the evidence adds up to
Optic nerve coloboma is a rare congenital anomaly caused by partial or complete failure of closure of the embryonic fissure, characterised by a sharply demarcated, bowl-shaped excavation that replaces part of the optic disc, most commonly involving the inferior nasal aspect and potentially extending to the retina, uvea, and sclera. The relative roles of genetics and environment in optic fissure closure remain elusive; while most cases are sporadic, autosomal dominant, autosomal recessive, and X-linked inheritance patterns have been described, and colobomata demonstrate pleiotropy, heterogeneity, variable expressivity, and reduced penetrance. In one 1976 study of a family with autosomal-dominant inheritance, 15 members had bilateral optic nerve colobomas appearing as enlargement of the physiologic cup, with severely affected eyes having huge cavities at the disc site; macular or extramacular serous detachment or sequelae occurred in 21 of 30 affected eyes and often led to total blindness. A 1988 report of four members across three generations found bilateral optic disk anomalies with variable expressivity: five of eight affected eyes had profound visual loss, but three eyes showed normal vision, and two cases developed unilateral nonrhegmatogenous retinal detachment.
In a 2015 study, coloboma severity was scored from 0 (normal) to 4 (large coloboma of the optic disc and adjacent retina, or morning glory anomaly). Patients with clinically diagnosed renal-coloboma syndrome and PAX2 gene mutations (n=11) had significantly higher mean coloboma scores than those without PAX2 mutations (n=15) and than disease controls with optic nerve coloboma but no kidney abnormality (n=4). CHD7 mutations have been identified in patients with CHARGE syndrome, which includes coloboma, but mutations in genes critical to eye development have been found in few individuals with coloboma overall. A 1930 review noted difficulty in classifying cases, with reports ranging from holes in the disk and extensive physiologic cup to coloboma of the nerve head associated with coloboma of the choroid, ciliary body, and iris.
No drug treatment for optic nerve coloboma is mentioned in any of these abstracts. What remains missing is any molecular understanding of the mechanisms leading to coloboma, which are still largely unknown; no clinical trial has tested a pharmacological intervention, and no patient stratification beyond genetic subtyping (PAX2, CHD7) has been linked to a therapeutic strategy. Funding for basic research on optic fissure closure and for any future trial design would be needed before a drug could be considered.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Ophthalmology · 2006 · 148 citations
Uveal coloboma: clinical and basic science update
AbstractPURPOSE OF REVIEW: To integrate knowledge on the embryologic and molecular basis of optic fissure closure with clinical observations in patients with uveal coloboma. RECENT FINDINGS: Closure of the optic fissure has been well characterized and many genetic alterations have been associated with coloboma; however, molecular mechanisms leading to coloboma remain largely unknown. In the past decade, we have gained better understanding of genes critical to eye development; however, mutations in these genes have been found in few individuals with coloboma. CHD7 mutations have been identified in patients with CHARGE syndrome (coloboma, heart defects, choanal atresia, retarded growth, genital anomalies, and ear anomalies or deafness). Animal models are bringing us closer to a molecular understanding of optic fissure closure. SUMMARY: Optic fissure closure requires precise orchestration in timing and apposition of two poles of the optic cup. The relative roles of genetics and environment on this process remain elusive. While most cases of coloboma are sporadic, autosomal dominant, autosomal recessive, and X-linked inheritance patterns have been described. Genetically, colobomata demonstrate pleiotropy, heterogeneity, variable expressivity, and reduced penetrance. Coloboma is a complex disorder with a variable prognosis and requires regular examination to optimize visual acuity and to monitor for potential complications.
Optic Nerve Colobomas of Autosomal-Dominant Heredity
AbstractFifteen members of a family had congenital colobomas of the optic nerves, all of which were bilateral. The bolobomas appeared as enlargement of the physiologic cup with severely affected eyes having huge cavities in the site of the disc. A variable amount of glial tissue was present within the colobomas. Either macular or extramacular serous detachment or sequelae were present in 21 of the 30 affected eyes, and often led to total blindness. Radioisotope cisternography in one patient failed to implicate cerebrospinal fluid as the source of the subretinal fluid. The disorder is apparently inherited as an autosomal dominant.
Archives of ophthalmology · 1930 · 33 citations · open access
BILATERAL COLOBOMA OF THE OPTIC NERVE
AbstractFrom an ophthalmoscopic examination of what is commonly termed coloboma of the optic nerve, it is difficult to tell whether the developmental defect is in the optic nerve or in the adjacent choroid. In a review of the literature, one encounters difficulty in classifying the cases, for there is wide latitude in many of the reports. Thus one finds the extremes—holes in the disk and extensive physiologic cup, to coloboma of the nerve head in association with coloboma of the choroid, ciliary body and iris. It is therefore impossible to tell accurately how many reports have been made, although one may have an idea from Crampton's<sup>1</sup>review in 1912, when he collected twenty-one cases in sixteen patients, which report included the six unequivocal examples recorded by Coates,<sup>2</sup>in all of which he had made histologic examinations. I found twenty-six additional cases (some very uncertain) with only
AbstractFour members of three consecutive generations of a family had congenital anomalies of the optic disk: deep excavation of the optic disk containing a mass of white glial tissue at its center, anomalous retinal vessels emerging from the peripheral aspect of the disk, and elevated annulus of peripapillary pigmentary disturbance. These optic disk anomalies occurred bilaterally with some inter- and intra-individual variable expressivity. Five of the eight affected eyes had profound visual loss, but three eyes showed normal vision. Two cases developed unilateral nonrhegmatogenous retinal detachment. There were no other ocular or systemic malformations. This family illustrates an instance of autosomal dominantly inherited optic nerve coloboma.
Journal of the Foundations of Ophthalmology · 2025 · 0 citations · open access
Optic Disc Coloboma
AbstractOptic disc coloboma is a rare congenital anomaly of the optic nerve head caused by partial or complete failure of closure of the embryonic fissure. It is characterised by a sharply demarcated, bowl-shaped excavation that replaces part of the optic disc. The defect most commonly involves the inferior nasal aspect of the disc and may extend to involve the retina, uvea, and sclera.
Optic nerve coloboma was severe in patients with <i>PAX2</i> mutations.
Abstract<p>Representative images of coloboma scores 0–4 are shown in <i>panel A</i>. Score 0, normal optic disc; Score 1, optic disc dysplasia with an unusual pattern of the retinal vessels and cilioretinal arteries; Score 2, optic disc pit associated with vascular abnormalities and a cilioretinal artery; Score 3, large coloboma involving the entire surface of the optic disc; Score 4, large coloboma of the optic disc and adjacent retina, or morning glory anomaly (with radial emergence of the retinal vessels). The mean coloboma scores of each group are shown in <i>panel B</i>. The coloboma scores (total, right and left eye) were significantly higher in patients with <i>PAX2</i> mutations. Values represent the mean ± SEM. *, p < 0.05 vs. coloboma scores of patients without <i>PAX2</i> mutations. “RCS with PAX2 mutations” indicates clinically diagnosed renal-coloboma syndrome cases with <i>PAX2</i> gene mutations (n = 11), “RCS without PAX2 mutations” indicates clinically diagnosed renal-coloboma syndrome cases without <i>PAX2</i> gene mutations (n = 15), and “Coloboma only” indicates cases with optic nerve coloboma and no kidney abnormality (a disease control; n = 4).</p>
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.
