DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for corneal dystrophy — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCorneal dystrophy maps to a 37-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 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
ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 3 (ST8SIA3) — ST8SIA3 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 ctpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5BO7 · 1.85 Å · ligand CYTIDINE-5'-TRIPHOSPHATE (CTP). Experimental structure, not a prediction.
What the evidence adds up to
Corneal dystrophy is a group of hereditary corneal diseases with varied pathology, histology and clinical manifestations. Recent advances in gene sequencing have improved understanding, but many aspects remain unknown and treatment results are not satisfactory, according to a 2016 review. A 1999 review noted that genetic heterogeneity (one disease caused by mutations in any of multiple genes) and phenotypic diversity (many diseases caused by mutations in a single gene) are common themes; for example, Meesmann dystrophy involves keratins 3 and 12, while mutations in keratoepithelin cause several distinct stromal and Bowman layer dystrophies. A 2016 review of IC3D category 1 dystrophies confirmed that clear genetic links exist for these, and that pathology involves structural disorganisation, aberrant protein stability, abnormal proliferation or apoptosis, and dysfunctional enzymatic processes.
For Avellino dystrophy, a combination of granular and lattice dystrophy, the first reported patient was treated with phototherapeutic keratectomy in 2010. For Fuchs endothelial corneal dystrophy, a 2017 study of phacoemulsification with central circular descemetorhexis in 63.8% of patients achieved visual rehabilitation without endothelial transplantation; mean central corneal pachymetry was 587.8±44.8 µm. A 2018 study of descemetorhexis combined with accelerated collagen crosslinking reported corneal state improvement and restoration of transparency in 66.6% of primary endothelial dystrophy cases, attributed to migration of endothelial cells from the periphery. In secondary endothelial dystrophy, the same method was ineffective, and the reasons for failure are not clear.
No drug treatment is described in any of these abstracts. What is missing is a molecular therapy or gene editing approach that targets the specific genetic mechanisms now identified; adequate funding for trials of such approaches; and patient stratification by genetic subtype, since the same clinical phenotype can arise from different genes and the same gene mutation can produce different diseases.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Ophthalmology · 2016 · 39 citations · open access
Characteristics of corneal dystrophies: a review from clinical, histological and genetic perspectives
AbstractCorneal dystrophy is a common type of hereditary corneal diseases. It includes many types, which have varied pathology, histology and clinical manifestations. Recently, the examination techniques of ophthalmology and gene sequencing advance greatly, which do benefit to our understanding of these diseases. However, many aspects remain still unknown. And due to the poor knowledge of these diseases, the results of the treatments are not satisfoctory. The purpose of this review was to summarize the clinical, histological and genetic characteristics of different types of corneal dystrophies.
In Vivo Confocal Microscopy of Fleck Dystrophy and Pre-Descemet's Membrane Corneal Dystrophy
AbstractPURPOSE: To assess the value of in vivo confocal microscopy (CM) in the diagnosis of Fleck dystrophy and pre-Descemet's membrane corneal dystrophy. METHODS: Case report of two patients. Standard slit-lamp and ophthalmic examination and in vivo CM were performed on both patients. The thickness of the cornea and the morphology of the corneal epithelium, stroma, endothelium, and subbasal nerves were evaluated by confocal microscopy. RESULTS: Biomicroscopy revealed bilateral, fine, dust-, and flour-like opacities in the corneal stroma for the Fleck dystrophy patient. In the pre-Descemet's membrane corneal dystrophy patient, biomicroscopy showed opacities larger than those in the first patient. Both patients were then examined by in vivo CM. Confocal microscopy of the Fleck dystrophy showed intracellular deposits throughout the stroma. In pre-Descemet's membrane corneal dystrophy, however, these and the extracellular deposits were observed immediately anterior to Descemet's membrane. The thicknesses of the corneas were 560 and 650 microm for Fleck and pre-Descemet's membrane corneal dystrophy, respectively. The surface epithelium, subbasal nerves, and endothelium showed normal morphology in both patients. CONCLUSION: In vivo CM is a valuable tool in diagnosing rare corneal dystrophies when the final diagnosis is difficult to obtain with conventional methods.
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.
Phototherapeutic Keratectomy in the Treatment of Avellino Dystrophy
AbstractAvellino corneal dystrophy has rarely been reported in literature. It consists of a combination of granular and lattice dystrophy. Patients may complain of glare and decreased night vision with or without decreased visual acuity, depending on the degree of corneal involvement. Current treatment for this dystrophy includes bandage contact lenses for the erosions or corneal transplant in the case of decreased visual acuity. We describe the first patient with Avellino corneal dystrophy to have been treated with phototherapeutic keratectomy.
Russian Annals of Ophthalmology · 2017 · 12 citations
Clinical and functional results of one-step phaco surgery and central descemetorhexis for cataract and Fuchs primary endothelial corneal dystrophy
AbstractPoor visual function associated with Fuchs endothelial corneal dystrophy (FECD) is one of the main indications for keratoplasty. Reports of successful visual rehabilitation of patients with spontaneous or scheduled removal of the Descemet's membrane and the endothelium or donor material adhesion failure, suggest this research direction perspective. AIM: to evaluate the potential as well as clinical and functional outcomes of phacoemulsification with central circular descemetorhexis in patients with Fuchs endothelial corneal dystrophy. MATERIAL AND METHODS: , and central corneal pachymetry - 587.8±44.8 µm. After phacoemulsification with IOL implantation, a 4 mm tap was created from the epithelial side of the cornea. Central circular descemetorhexis was done using a microhook. The membrane was removed with microforceps. RESULTS: . CONCLUSION: In 63.8% of patients, visual rehabilitation was achieved without endothelial transplantation, which provides new prospects for tissue-saving technologies in patients with endothelial corneal dystrophy.
Asia-Pacific Journal of Ophthalmology · 2016 · 7 citations
The Genetics and Pathophysiology of IC3D Category 1 Corneal Dystrophies
AbstractCorneal dystrophies are a group of inherited disorders affecting the cornea, many of which lead to visual impairment. The International Committee for Classification of Corneal Dystrophies has established criteria to clarify the status of the various corneal dystrophies, which include the knowledge of the underlying genetics. In this review, we discuss the International Committee for Classification of Corneal Dystrophies category 1 (second edition) corneal dystrophies, for which a clear genetic link has been established. We highlight the various mechanisms underlying corneal dystrophy pathology, including structural disorganization, instability or maladhesion, aberrant protein stability and deposition, abnormal cellular proliferation or apoptosis, and dysfunction of normal enzymatic processes. Understanding these genetic mechanisms is essential for designing targets for therapeutic intervention, especially in the age of gene therapy and gene editing.
Ophthalmology Reports · 2018 · 4 citations · open access
About a new approach to surgical treatment of corneal endothelial dystrophy
AbstractPrimary endothelial dystrophy of the cornea is a fairly common disease in people older than 50 years. Well-developed methods of conservative treatment, as a rule, do not lead to improvement or stabilization of the functional state of the cornea. The choice of tactics of surgical treatment from the existing variety of techniques is complicated. There are isolated reports of the restoration of corneal transparency after descemet membrane removal. The author's method of endothelial corneal dystrophy treatment addressed in this particular clinical case a combination of isolated descemetorhexis and collagen cross-linking resulted in impressive increase in visual acuity and significant improvement in objective criteria for the morpho-functional state of the cornea.
Ophthalmology Reports · 2018 · 1 citations · open access
Comparative assessment of the efficacy of primary and secondary corneal endothelial dystrophy treatment by isolated descemetorhexis and accelerated collagen crosslinking method
AbstractThe article examines the efficacy of the authors method of endothelial corneal dystrophy treatment, inclu ding descemetorhexis and accelerated collagen crosslinking. In primary endothelial dystrophy, corneal state improvement and restoration of its transparency were observed in 66.6% of cases (due to migration of endothelial cells from the periphery to the сentral zone). In secondary endothelial dystrophy, the treatment method described in the present article is ineffective, and the reasons for failures are not quite clear and require further investigation.
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.
