DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cornea plana — 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 moduleCornea plana 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 cornea plana 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.
What the evidence adds up to
Congenital cornea plana occurs in two hereditary forms: an autosomal dominant form with relatively mild symptoms and an autosomal recessive form with more severe symptoms. In Finland, 49 cases of the recessive and seven of the dominant form have been discovered, about twice the number of recessive cases reported elsewhere in the world. In Finnish Lapland, the gene frequency of the recessive form is estimated at 1.3% (about 16 patients per 100,000 inhabitants), roughly four times the rate for Finland as a whole. A pedigree around the lower reaches of the River Kemijoki includes 25 related patients. The vast majority of cases are in individuals of Finnish descent, but the disease also occurs in other populations: a Cuban family with dominant cornea plana and a Hispanic family with recessive cornea plana have been reported.
In the recessive form, affected individuals show extreme corneal flattening (keratometry readings below 36 diopters, and in one Czech family below 30 D), hyperopia greater than 6.25 D spherical equivalent (often 10 D or more), and normal axial eye lengths. Anterior segment abnormalities include scleralization of the cornea, central iris strands to the corneal endothelium, hazy limbus, corneal parenchymal opacities, and marked arcus senilis detectable at an early age. In a Czech family, two siblings were compound heterozygotes for two novel KERA mutations: a missense mutation c.209C>T (p.Pro70Leu) and a splice site mutation c.887-1G>A. One of these siblings, aged 20, showed marked thinning with protrusion in the superior part of the left cornea, resulting in mean keratometry of 47.2 D — a very rare finding whose possible progressivity requires longitudinal follow-up. In a nuclear family, five of six siblings were affected and had a novel homozygous nonsense mutation in exon 3 (937C>T), replacing arginine with a stop codon at position 313 of keratocan. In a Hispanic family, affected individuals were homozygous for a mutation in exon 2 (asparagine to aspartic acid at codon 131), falling within a highly conserved leucine-rich repeat.
In the dominant form, corneal refraction varies between 37.50 and 42.75 diopters, horizontal corneal diameter ranges from 8.75 to 11.25 mm, the cornea is clear, and the limbal zone is only occasionally widened. A marked arcus senilis was present in six patients aged 30 to 58 years but in none of their healthy relatives. The anterior chamber is shallow (depth 1.68 to 2.38 mm), and one woman was blind from closed-angle glaucoma. Axial length is within normal limits. In a case of bilateral cornea plana with unilateral microcornea and open-angle glaucoma, the patient's glaucoma was stable on a single anti-glaucoma medication, but the authors note that intraocular pressure measurement can be biased due to varied corneal morphology.
What is still missing: systematic longitudinal data on the progression of corneal thinning and protrusion in the rare cases where it occurs; a clear understanding of how to reliably measure intraocular pressure in these abnormally shaped corneas; and any treatment trial — no drug or surgical intervention has been tested in a controlled fashion for cornea plana itself. The condition remains defined by descriptive genetics and case series, with no stratification of patients by mutation type or severity to guide 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.
Clinical Genetics · 1973 · 34 citations
Congenital cornea plana in Finland
AbstractTwo different hereditary forms of congenital cornea plana are described: an autosomal dominant form with relatively mild symptoms, and an autosomal recessive form (CPCR) with more severe symptoms, such as decreased visual acuity, extreme hyperopia (total refraction usually 10 D or more), hazy limbus corneae, more or less pronounced opacities in the corneal parenchyma, and marked arcus senilis, often detectable at an early age. As far as can be judged from the number of cases hitherto published, cornea plana is a rare disease. In Finland, 49 caw of the recessive and seven of the dominant form of cornea plana congenita have been discovered to date, which is about twice the number of cases of recessively inherited cornea plana reported elsewhere in the world. In Finnish Lapland, the gene frequency of cornea plana congenita recessiva is estimated to be 1.3 % (about 16 patients per 100,000 inhabitants), or about four times as high as in Finland as a whole. Around the lower reaches of the River Kemijoki there is a relatively high prevalence of the recessive form of the disease. The Kemijoki pedigree includes 25 patients related to each other through their ancestors.
A novel<i>KERA</i>mutation associated with autosomal recessive cornea plana
AbstractPURPOSE: To report a novel KERA mutation associated with autosomal recessive cornea plana in members of a nuclear family and to describe their ophthalmic phenotypes. METHODS: Ophthalmic examination, biometry, and direct sequencing of KERA. RESULTS: Five of the 6 siblings were affected and had small flat corneas, variable anterior chamber depths, and short axial lengths. The remaining brother and the 2 parents had normal ophthalmic examinations. Genetic testing revealed a novel homozygous nonsense mutation in exon 3 [937C>T] in the clinically affected individuals. The clinically unaffected parents were confirmed as carriers. The clinically unaffected sibling had no KERA mutation. This mutation leads to replacement of an arginine by a stop codon at position 313 of keratocan protein. CONCLUSIONS: This novel point mutation in KERA is the fourth thus far described. The ocular phenotype is characteristic of autosomal recessive cornea plana.
Clinical and Molecular Characterization of a Family With Autosomal Recessive Cornea Plana
AbstractBACKGROUND: Autosomal recessive cornea plana is characterized by a flattened corneal surface associated with hyperopia and various anterior segment abnormalities. Mutations have been detected in the keratocan gene (KERA), a member of the small leucine-rich proteoglycan family. OBJECTIVE: To clinically and molecularly characterize a consanguineous family of Hispanic origin in which 3 individuals are affected with cornea plana. METHODS: Clinical ophthalmic examination, including corneal topography and axial eye length measurement, was performed on 7 family members. Molecular analysis of KERA was performed on DNA from each family member who had been examined. RESULTS: All 3 affected individuals showed extreme flattening of the cornea (< 36 diopters [D]), normal axial eye lengths, and hyperopia greater than 6.25 D (spherical equivalent). Anterior segment abnormalities included scleralization of the cornea and central iris strands to the corneal endothelium. Affected individuals were homozygous for a novel mutation in KERA. The sequence change was found in exon 2, which results in an asparagine to aspartic acid change at codon 131. This amino acid change occurs within a highly conserved leucine-rich repeat of keratocan. CONCLUSIONS: The cause of disease in this family is likely to be a mutation in exon 2 of KERA. Other mutations in KERA known to cause cornea plana also fall within the region encoding the leucine-rich repeat motifs and are predicted to affect the tertiary structure of the protein. CLINICAL RELEVANCE: This is the first report of the identification of a mutation within KERA in a family of Hispanic origin with autosomal recessive cornea plana. Although the vast majority of cases of cornea plana are in individuals of Finnish descent, this report demonstrates the occurrence of the disease in other populations.
Autosomal dominant cornea plana: Clinical findings in a Cuban family and a review of the literature
AbstractCornea plana may occur in connection with malformations of the eye or of other parts of the body. As an isolated ocular anomaly, it may be inherited in an autosomal recessive or in an autosomal dominant fashion. We have previously mapped genes for both forms of the disease to 12q21. We studied 36 members of three generations of a Black Cuban family with autosomal dominant cornea plana. Three affected males and 11 affected females were examined. Corneal refraction varied between 37.50 and 42.75 diopters. Horizontal corneal diameter ranged from 8.75 to 11.25 mm. The cornea was clear and the limbal zone only occasionally widened. A marked arcus senilis was present in six patients aged 30 to 58 years, but in none of their healthy relatives. The anterior chamber was shallow in those affected, varying in depth from 1.68 to 2.38 mm. One woman was blind from closed-angle glaucoma. The axial length was within normal limits in all patients.
Indian Journal of Ophthalmology - Case Reports · 2021 · 3 citations · open access
Open-angle glaucoma in a case of cornea plana with unilateral microcornea
AbstractCornea plana is a rare congenital condition, usually occurring bilaterally, characterized by flat cornea and low refractive power. Glaucoma due to angle closure is a more common association owing to the shallow anterior chamber. We report a case of an elderly lady with bilateral cornea plana with immature cataract and open-angle glaucoma, and unilateral microcornea. The patient is visually rehabilitated. Her glaucoma is stable, maintained on a single anti-glaucoma medication. In conclusion, IOP measurement in these patients can be biased due to varied corneal morphology. However, with proper evaluation, these challenging cases can be well managed.
Two novel KERA mutations causing cornea plana in a Czech family and associated phenotypes
AbstractPurpose To identify the molecular genetic cause in a previously not reported Czech family with the occurrence of cornea plana in two siblings. Methods Detailed ophthalmological examination and direct sequencing of the KERA coding region in the proband followed by target analysis of the identified mutations in other family members. Results The family was not aware of any consanguinity. Compound heterozygosity for a novel missense mutation c.209C>T; p.(Pro70Leu) and a novel splice site mutation c.887‐1G>A in KERA were detected in both affected individuals. The mother was a heterozygous carrier of c.887‐1G>A and the father of c.209C>T. In silico analysis supported the pathogenicity of both mutations. The younger brother, aged 13 years, had typical ocular phenotype of cornea plana with keratometry readings bellow 30 D, shallow anterior chamber, indistinct limbus and central corneal opacity. Corneal endothelial cell morphology was normal in the right eye; in the left eye specular microscopy images could not be taken. In the older brother, aged 20 years, marked thinning with protrusion in the superior part of the left cornea was present resulting into mean keratometry of 47.2 D. No corneal endothelial cell pathology was observed by specular microscopy bilaterally. Conclusions The identification of two novel heterozygous mutations in the second Czech family with cornea plana does not support the hypothesis of a founder effect. Marked corneal thinning and protrusion in cornea plana is a very rare finding and longitudinal follow‐up evaluation needs to be performed to determine its possible progressivity.
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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