DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital stromal corneal dystrophy — 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 moduleCongenital stromal corneal dystrophy 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 congenital stromal corneal dystrophy 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
SPARC like 1 (SPARCL1) — SPARCL1 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 7KBU · 2.27 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2002 report of a mother and son with bilateral congenital corneal clouding found a thickened stroma with diffuse small opacities present at birth and slowly progressive; visual acuity was reduced to 2/10. Electron microscopy of the excised corneas showed a thickened stroma due to cleaving of the lamellae by alternating layers of small-diameter collagen fibrils arranged randomly, while epithelium, Bowman's membrane, endothelium, and Descemet's membrane were normal. This family's congenital stromal dystrophy was not linked to endothelial defects, differing from the more common congenital hereditary corneal endothelial dystrophy. A 1969 study of two separate pedigrees with dominant inheritance of a congenital nonprogressive corneal clouding found the same characteristic changes of abnormal corneal lamellae widely and uniformly distributed throughout the stroma, with all other corneal layers normal, consistent with a diagnosis of congenital hereditary stromal dystrophy that differs greatly on histologic and clinical grounds from congenital hereditary endothelial dystrophy.
A 1999 review noted that genetic heterogeneity and phenotypic diversity are common in corneal dystrophies. Mutations in a single gene, keratoepithelin (now TGFBI), were found to cause several distinct corneal dystrophies affecting the Bowman layer and the stroma. A 2006 study of a 60-year-old woman with classic granular stromal corneal dystrophy type I and her affected brother found a point mutation in exon 14 of the TGFBI gene, an adenine to guanine change at nucleotide 1924 predicting a substitution of arginine for histidine at residue 626 (H626R). This mutation had classically been detected in the phenotypically distinct lattice corneal dystrophy, indicating that the same molecular defect in TGFBI leads to different phenotypes in stromal dystrophies.
A 2017 case report on granular corneal dystrophy type 1 reiterates that most dystrophies previously considered stromal are now classified as either epithelial-stromal or stromal dystrophies, caused by genetic mutations leading to transcription of aberrant proteins and accumulation of insoluble material within the cornea, not by inflammation, infection, or trauma. No treatment beyond corneal transplantation is described in any of these abstracts, and no drug is mentioned for congenital stromal corneal dystrophy. What is still missing is any molecular characterisation of the specific genetic defect in congenital hereditary stromal dystrophy, any animal model, any drug screening effort, and any clinical trial design for a 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.
Cornea · 2002 · 29 citations
Report of a New Family with Dominant Congenital Heredity Stromal Dystrophy of the Cornea
AbstractPURPOSE: To report a new family with the rare form of congenital and hereditary stromal dystrophy of the cornea. METHODS: A mother and son, showing a bilateral congenital clouding of the cornea, were studied clinically and by biomicroscopy. After corneal transplantation, light microscopy and electron microscopy were performed. RESULTS: The stroma of the cornea was bilaterally and symmetrically thickened with diffuse and homogeneous small opacities. The opacities were present at birth and slowly progressive. Visual acuity was reduced to 2/10. Electron microscopy of the excised corneas showed a thickened stroma owing to cleaving of the lamellae by alternating layers of small-diameter collagen fibrils arranged in a random fashion. The epithelium, Bowman's membrane, the endothelium, and Descemet's membrane were normal. CONCLUSIONS: This family presents with a congenital stromal dystrophy of the cornea not linked to endothelial defects and thus differs from the more common form of congenital hereditary corneal endothelial dystrophy.
Current Opinion in Ophthalmology · 1999 · 26 citations
A new clinical perspective of corneal dystrophies through molecular genetics
AbstractIn the past 2 years, significant advances have been made in the genetics of corneal dystrophies. Genetic heterogeneity (one disease condition caused by single mutations in any one of multiple genes) and phenotypic diversity (many disease conditions caused by mutations in a single gene) are common emerging themes. Genetic heterogeneity in Meesmann corneal dystrophy was established with the identification of two causative genes, keratins 3 and 12, that encode cytoskeletal proteins. Conversely, mutations in a single gene, keratoepithelin, were found to cause several distinct corneal dystrophies affecting the Bowman layer and the stroma. We present a novel preliminary classification of corneal dystrophies based on molecular etiology. This classification may be useful in understanding the pathogenesis of corneal dystrophies and in developing new strategies to treat these dystrophies.
Archivos de la Sociedad Española de Oftalmología · 2006 · 8 citations · open access
Distrofia corneal granular autosómica dominante causada por mutación del gen TGFBI en una familia mexicana
AbstractOBJECTIVE: To describe the clinical data and the results of molecular analyses of the TGFBI gene in a patient with classic granular stromal corneal dystrophy (type I). METHODS: A female patient aged 60-years complaining of a long-standing decrease of visual acuity bilaterally associated with photophobia and foreign body sensation, underwent a complete ophthalmologic examination. Molecular analyses of DNA from the patient and from an affected brother included PCR amplification of exons 4, 11, 12, and 14 of the TGFBI gene and direct automated sequencing of the PCR products. RESULTS: The affected patient showed a pattern of corneal stromal lesions that was compatible with a diagnosis of classic granular dystrophy. No involvement of other corneal layers was evident. Molecular analysis disclosed a point mutation in exon 14 of the TGFBI gene which consisted of an adenine to guanine change at nucleotide position 1924, predicting a substitution of arginine instead of histidine at residue 626 of the TGFBI protein (H626R). An identical mutation was detected in DNA from her affected brother. CONCLUSIONS: This is the first time that a case of stromal granular dystrophy has been demonstrated to be caused by the H626R mutation, a molecular defect classically detected in the phenotypically distinct lattice corneal dystrophy. Our data indicate that the same molecular defects in the TGFBI gene lead to different phenotypes in stromal dystrophies, thus expanding the genotypic-phenotypic spectrum in this group of corneal diseases.
Transactions of the American Nuclear Society · 1969 · 0 citations
TECHNIQUES FOR ALPHA-MEASUREMENT USING NULL-REACTIVITY METHODS IN FAST CRITICAL ASSEMBLIES.
AbstractCornea from patients in two separate pedigrees showing dominant inheritance of a congenital nonprogressvie corneal clouding were examined by light and electron microscopy. The characteristic changes of abnormal corneal lamellae were widely and rather uniformly distributed throughout the stroma. The remaining corneal layers were normal. The findings are consistent with a diagnosis of congenital hereditary stromal dystrophy of the cornea, which differs greatly on both histologic and clinical grounds from the entity known as congenital hereditary endothelial dystrophy of the cornea.
An Interesting Case of Granular Corneal Dystrophy Type 1
AbstractCorneal epithelial-stromal and stromal dystrophies are a group of inherited disorders of the cornea that are caused by progressive accumulation of deposits within the layers of the cornea. Most dystrophies previously considered stromal are now classified as either epithelial-stromal dystrophies or stromal dystrophies. These deposits are not caused by inflammation, infection, or trauma, but by genetic mutations that lead to transcription of aberrant proteins resulting in the accumulation of insoluble material within the cornea. Hereby author intends to report an interesting case of granular corneal dystrophy type 1.
Indian Journal of Clinical and Experimental Ophthalmology · 2022 · 0 citations · open access
Atypical presentation of macular corneal dystrophy
AbstractA 65-year old male patient presented to our ophthalmology OPD for regular check up. On examination visual acuity of the right eye was 6/24 improving to 6/12p with pinhole and left eye was 6/18 improving with pinhole 6/9. On examination of anterior segment both eyes cornea showed multiple white round deposits at deep posterior stroma and Descemet membrane – endothelium complex scattered circumferentially in the peripheral cornea and the central cornea clear and lens showed Immature cataract. Fundus examination was within normal limits. A differential diagnosis of stromal corneal dystrophy or endothelial corneal dystrophy was made. By exclusion, we came to the diagnosis of macular corneal dystrophy.
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.
