DeCure for Spondylometaphyseal dysplasia with corneal dystrophy
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spondylometaphyseal dysplasia with corneal dystrophy — 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 moduleSpondylometaphyseal dysplasia with corneal dystrophy 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 spondylometaphyseal dysplasia with 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
phospholipase C beta 3 (PLCB3) — PLCB3 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8UQO · 3.37 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
A 2010 report on twin females with spondylometaphyseal dysplasia and cone-rod dystrophy found that the ocular manifestations appeared to stabilise in early adolescence, while the skeletal abnormalities were progressive with age. The twins had fine nystagmus by 10 months of age, and fundus examination showed bilateral, large, excavated, well-circumscribed oval areas of chorioretinal atrophy in the macula. Electroretinography showed a significant reduction in photopic responses and a slight reduction in scotopic components, consistent with cone-rod dystrophy. The report described the disorder as rare and of unknown inheritance pattern and pathophysiology.
A 2016 review of corneal dystrophies stated that many aspects of these diseases remain unknown and that treatment results are not satisfactory. The review summarised clinical, histological, and genetic characteristics of different types of corneal dystrophies but did not address spondylometaphyseal dysplasia.
A 2018 study tested five ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) for their ability to correct SLC4A11 protein misfolding in cell models of Fuchs' endothelial corneal dystrophy and congenital hereditary endothelial dystrophy. In HEK293 cells, diclofenac and nepafenac moved endoplasmic reticulum-retained missense mutant SLC4A11 to the cell surface. Among 30 intracellular-retained SLC4A11 mutants, 20 had significant restoration of cell surface abundance with diclofenac. Diclofenac restored mutant SLC4A11 water flux activity to wild-type levels in some cases. The authors encouraged testing diclofenac eye drops in patients whose corneal dystrophy is caused by some SLC4A11 missense mutations. No study has tested any drug in patients with spondylometaphyseal dysplasia with corneal dystrophy, and no link between SLC4A11 and this specific syndrome has been reported.
A 2006 comparison of confocal microscopes for imaging corneal dystrophies found both devices provided helpful diagnostic information, with no essential qualitative differences between them. This technical study did not address treatment or the specific disease in question. What is still missing is any clinical trial, any patient-derived data on drug response, any understanding of the genetic basis of spondylometaphyseal dysplasia with corneal dystrophy, and any funding directed at this specific rare disorder.
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.
Ophthalmic Nonsteroidal Anti-Inflammatory Drugs as a Therapy for Corneal Dystrophies Caused by SLC4A11 Mutation
AbstractPurpose: SLC4A11 is a plasma membrane protein of corneal endothelial cells. Some mutations of the SLC4A11 gene result in SLC4A11 protein misfolding and failure to mature to the plasma membrane. This gives rise to some cases of Fuchs' endothelial corneal dystrophy (FECD) and congenital hereditary endothelial dystrophy (CHED). We screened ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) for their ability to correct SLC4A11 folding defects. Methods: Five ophthalmic NSAIDs were tested for their therapeutic potential in some genetic corneal dystrophy patients. HEK293 cells expressing CHED and FECD-causing SLC4A11 mutants were grown on 96-well dishes in the absence or presence of NSAIDs. Ability of NSAIDs to correct mutant SLC4A11 cell-surface trafficking was assessed with a bioluminescence resonance energy transfer (BRET) assay and by confocal microscopy. The ability of mutant SLC4A11-expressing cells to mediate water flux (SLC4A11 mediates water flux across the corneal endothelial cell basolateral membrane as part of the endothelial water pump) was measured upon treatment with ophthalmic NSAIDs. Results: BRET-assays revealed significant rescue of SLC4A11 mutants to the cell surface by 4 of 5 NSAIDs tested. The NSAIDs, diclofenac and nepafenac, were effective in moving endoplasmic reticulum-retained missense mutant SLC4A11 to the cell surface, as measured by confocal immunofluorescence. Among intracellular-retained SLC4A11 mutants, 20 of 30 had significant restoration of cell surface abundance upon treatment with diclofenac. Diclofenac restored mutant SLC4A11 water flux activity to the level of wild-type SLC4A11 in some cases. Conclusions: These results encourage testing diclofenac eye drops as a treatment for corneal dystrophy in patients whose disease is caused by some SLC4A11 missense mutations.
Klinische Monatsblätter für Augenheilkunde · 2006 · 10 citations
Konfokale Scanning-Mikroskopie: Eine vergleichende Darstellung von Hornhautdystrophiebefunden mittels ConfoScanP2 und Rostock Cornea Modul-HRT II
AbstractBACKGROUND: The object of this work was a comparison of confocal images of corneal dystrophies made by a slit scanning microscope versus a laser scanning microscope. MATERIAL AND METHODS: Using the Rostock Cornea Modul-HRT II as a confocal laser scanning microscope the images of five patients with some epithelial, stromal and endothelial corneal dystrophies were acquired. The pictures were compared qualitatively with those taken by the slit scanning microscope "ConfoScan P2" from corresponding pathologies. Also, the images of normal corneas of ten healthy persons were acquired for a qualitative comparison. RESULTS: Confocal images from both devices were able to provide significant helpful diagnostic findings about the corneal microstructure. Essential qualitative differences between the images of both devices used were not observed. Due to the additional hardware components and the software module for image acquisition, analysis and archiving, the RCM-HRT II is favoured over the "ConfoScan P2". Nevertheless, the evaluation in favour of the RCM-HRT II has to be confined because an optimised, user-friendly enhancement, the "ConfoScan 4" is currently available. CONCLUSION: Evaluating corneal dystrophies in vivo, an equivalent utility of both technical approaches has been observed.
Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy
AbstractPURPOSE: To report on the clinical ophthalmologic and radiographic findings in spondylometaphyseal dysplasia with cone-rod dystrophy. BACKGROUND: The spondylometaphyseal dysplasias are a rare and heterogeneous group of disorders characterized by skeletal abnormalities of the spine and the metaphyses of long bones. In rare instances, spondylometaphyseal dysplasia can occur concomitantly with ocular abnormalities including a retinal degeneration of the cone-rod dystrophy type. METHODS: Retrospective review of affected twin females with serial radiographic imaging, comprehensive ophthalmologic examination, fundus photography, and electroretinography. RESULTS: The major radiographic findings involved bony abnormalities of the spine, metaphyses of the long bones and a distinctive shape to the bony pelvis. Both twins had a fine nystagmus that was present by 10 months of age. Dilated ocular fundus examination revealed similar appearing bilateral, large, excavated, well-circumscribed oval areas of chorioretinal atrophy occupying the macula between the aracades. Electroretinography showed a significant reduction in the photopic responses and slight reduction in the scotopic component of the waveforms consistent with cone-rod dystrophy. CONCLUSIONS: Spondylometaphyseal dysplasia with cone-rod dystrophy is a rare congenital disorder of unknown inheritance pattern and pathophysiolgy. The ocular manifestations appear to stabilize in early adolescence whereas the skeletal abnormalities are progressive with age.
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.
