DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for granular corneal dystrophy type II — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGranular corneal dystrophy type II maps to a 1-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 granular corneal dystrophy type ii 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
transforming growth factor beta induced (TGFBI) — TGFBI 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 5NV6 · 2.93 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1990 case report describes a patient who was most likely homozygous for the dominantly inherited granular corneal dystrophy gene, born to a first-cousin marriage with both parents mildly affected. The patient had early onset and a severe course, requiring two grafts in each eye before age 17. In 2005, two Indian families with severe granular corneal dystrophy were genotyped; a C→T mutation at residue 1710 of TGFBI cDNA, corresponding to an Arg555Trp mutation in keratoepithelin, was found in all affected members. Five patients were homozygous for this mutation and four were heterozygous. Homozygous individuals had early onset and superficial lesions, while heterozygous individuals had a milder phenotype. Histopathology from two homozygous patients confirmed superficial granular deposits.
A 2006 report of a 53-year-old male with severe corneal granular dystrophy found that a severe course can occur without evidence of a homozygous mutational status or a novel mutation; molecular genetic analysis revealed a new polymorphism. Histopathologic evidence supported an epithelial origin of the granular deposits. The same report stated that phototherapeutic keratectomy and penetrating keratoplasty may improve vision but cannot prevent recurrence. Two further case reports from 2006 described recurrent granular dystrophy in corneal grafts after penetrating keratoplasty; confocal microscopy showed that dystrophic lesions in the donor cornea had the same microscopic aspects as the original lesions, and the authors noted the method may be useful for early diagnosis of recurrence in grafts.
No drug treatment is mentioned in any of these abstracts. The evidence shows that recurrence after surgery is expected, that homozygous mutations produce a severe early phenotype, and that even heterozygous or apparently sporadic cases can follow a severe course. What is missing is any trial of a pharmacological intervention, any attempt to prevent or slow the accumulation of corneal deposits, and any patient stratification beyond the known TGFBI genotype that could guide such an attempt. Funding for drug-repurposing screens in corneal dystrophy models, or for a prospective natural-history study that could support a future trial, has not been reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cornea · 2015 · 62 citations
Planned Descemetorhexis Without Endothelial Keratoplasty in Eyes With Fuchs Corneal Endothelial Dystrophy
AbstractPURPOSE: The purpose of this study was to describe the results of a simple 6-mm central descemetorhexis in eyes with Fuchs corneal endothelial dystrophy. METHODS: This prospective nonrandomized IRB approved pilot study was performed on 2 patients with coexisting Fuchs dystrophy and cataract who underwent combined phacoemulsification and descemetorhexis without endothelial transplantation. RESULTS: In each patient, residual disciform stromal edema corresponded to the diameter of the descemetorhexis and led to an associated loss of visual acuity. Vision improved to 20/40 -1 in case 1 and to 150 -1 in case 2 during a follow-up period of 12 and 10 months, respectively. Endothelial cell repopulation of the descemetorhexis could not be confirmed because of the presence of persistent corneal edema. CONCLUSIONS: Because of the relatively poor postoperative visual acuity and slow visual recovery, a simple descemetorhexis is not an acceptable form of therapy for eyes with Fuchs corneal endothelial dystrophy.
AbstractA case of severe granular corneal dystrophy is described. The patient, who is most probably homozygous for the dominantly inherited dystrophy gene, is the product of a first cousin marriage with both parents mildly affected by the same dystrophy. The case report describes an early onset and a severe course with two grafts in each eye before the age of 17. Pictures of the clinical appearance, histology and transmission electronmicroscopy are shown.
AbstractPURPOSE: To describe a case of severe corneal granular dystrophy with clinicopathologic and molecular genetic findings. METHODS: The DNAs of a 53-year-old male patient suffering from corneal granular dystrophy and nonaffected family members were analyzed by molecular genetic methods. Clinical features, and histopathologic and immunohistochemical findings from the penetrating keratoplasty specimen, are described. RESULTS: Histopathologic and molecular genetic findings confirmed the diagnosis. A new genetic polymorphism is described. Histopathologic evidence supports the assumption of the epithelial origin of the described dystrophy. CONCLUSIONS: A severe course of corneal granular dystrophy can be present in the absence of evidence of a homozygous mutational status, or a novel mutation. Molecular genetic analysis revealed a new polymorphism in this patient. The histopathologic findings support the assumption of an epithelial origin of the granular corneal deposits. Phototherapeutic keratectomy and penetrating keratoplasty may improve vision, but cannot prevent recurrence of the disease.
Clinical and Experimental Ophthalmology · 2006 · 18 citations
<i>In vivo</i> confocal microscopy in recurrent granular dystrophy in corneal graft after penetrating keratoplasty
AbstractTwo case reports of recurrent granular dystrophy in corneal grafts after penetrating keratoplasty are presented. Slit-lamp examination and confocal microscopy (HRT II) were performed in two patients with recurrent granular dystrophy. All confocal microscopic findings of granular dystrophy were evaluated in the graft. Dystrophic lesions of the donor cornea presented the same confocal microscopic aspects in both eyes, and were similar to granular dystrophy lesions. Confocal microscopy is an imaging method that may provide new information on corneal microanatomy in dystrophies. It may be particularly useful in improving the early diagnosis of dystrophic lesions in corneal grafts.
Archives of Ophthalmology · 2005 · 16 citations · open access
Genotype-Phenotype Correlation in 2 Indian Families With Severe Granular Corneal Dystrophy
AbstractOBJECTIVES: To determine genotypes in 2 Indian families with severe granular corneal dystrophy, to document clinical and histopathologic features, and to attempt a genotype-phenotype correlation. METHODS: Mutation analysis of exon 12 of the TGFBI gene was carried out in 9 individuals from 2 families. RESULTS: A C-->T mutation at residue 1710 of TGFBI complementary DNA, corresponding to an Arg555Trp mutation in keratoepithelin, was found in affected members of both families. In 5 patients, this mutation was homozygous, and it was heterozygous in the other 4. Clinical examination revealed a severe form of granular corneal dystrophy with early onset and superficial lesions in the homozygous individuals and a milder phenotype in the heterozygous individuals. Histopathologic evaluation of corneal specimens from 2 homozygous patients confirmed the presence of superficial granular deposits. CONCLUSIONS: To our knowledge, this is the first molecular and clinical characterization of severe granular corneal dystrophy in India. Genotype-phenotype correlation and comparison with earlier reports on this entity highlight the uniform expressivity of the Arg555Trp allele in homozygous individuals. CLINICAL RELEVANCE: Homozygous granular corneal dystrophy has a severe phenotype and can be recognized based on clinical and histopathologic features, especially in association with consanguinity or inbreeding.
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.
