DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cataract 13 with adult I phenotype — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCataract 13 with adult I phenotype maps to a 13-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 cataract 13 with adult i phenotype 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
crystallin gamma D (CRYGD) — CRYGD 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 mnbdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9G3W · 1.8 Å · ligand 5-MERCAPTO-2-NITRO-BENZOIC ACID (MNB). Experimental structure, not a prediction.
What the evidence adds up to
A 2020 review notes that 115 genes have been associated with syndromic and non-syndromic cataract, with 38 disease-causing genes identified for isolated cataract. The same review discusses future therapeutic avenues including cellular therapies and pharmacological treatments, but provides no data on any drug tested in patients.
A 2020 study of Cohen syndrome, caused by VPS13B variants, generated Vps13b∆Ex3/∆Ex3 mice. Cataracts developed rapidly in 2-month-old knockout mice and were present in almost all lenses by 3 months. Cataract formation was associated with large vacuoles in the cortical area, epithelial-mesenchymal transition, and fibrosis. Later stages showed hypermature cataracts and retinal remodelling due to inflammation. A subline of the same knockout model showed delayed cataract onset, indicating that additional genetic factors modify the timing. No drug intervention was tested.
A 2022 review of GJA3 and GJA8 gap junction gene variants states that these two genes account for up to 18% of inherited paediatric cataract cases, second only to crystallin genes. Autosomal dominant inheritance is most frequent, with instances of reduced penetrance and autosomal recessive disease. Nearly half of the gap junction gene variants observed in cataract patients lack sufficient evidence of pathogenicity to form a useful clinical opinion. The authors note that generating well-characterised functional data for each variant would accelerate classification, but no such standardised data exist.
A 2018 study of 1052 Korean adults aged 40 or older found a J-shaped association between serum total IgE levels and age-related cataract. Compared to the reference range of 35–87 kU/L, participants with IgE ≥267 kU/L had an odds ratio of 2.00 (95% CI 1.22–3.27) for any cataract, and those with IgE ≤35 kU/L had an odds ratio of 1.67 (95% CI 1.02–2.72). High total IgE (>150 kU/L) gave an odds ratio of 1.48 (95% CI 1.03–2.13) for any cataract. This is an epidemiological association, not a drug study.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Respirology · 2009 · 95 citations
Dose–response relationship of inhaled corticosteroids and cataracts: A systematic review and meta‐analysis
AbstractBACKGROUND AND OBJECTIVE: The risk of cataracts associated with the long-term use of inhaled corticosteroids (ICS) is poorly recognized, yet may be of major public health importance. The aim of this study was to determine the dose-response relationship of ICS use and risk of cataracts in adults. METHODS: A systematic review and meta-analysis was performed of case-control studies of cataracts and ICS use, which included at least two doses of ICS and in which the number of cases and controls using each dose of ICS was reported. The primary outcome variable was risk of cataracts. RESULTS: Four case-control studies were identified, with a total of 46 638 cases and 146 378 controls. There was a significant relationship between the risk of cataracts and ICS dose, with a random effects pooled odds ratio for risk of cataracts per 1000 microg increase in daily beclomethasone dipropionate dose of 1.25 (95% CI: 1.14-1.37). CONCLUSIONS: The risk of cataracts was increased by approximately 25% for each 1000 microg per day increase in the dose of beclomethasone dipropionate or equivalent. These findings reinforce the importance of prescribing within the therapeutic dose-response range for ICS in asthma and the need to determine the dose-response relationship for the efficacy of ICS in COPD. Screening for the presence of cataracts could usefully be undertaken in older subjects with asthma and COPD, particularly current or ex-smokers.
AbstractCataract is the most common cause of blindness in the world; during infancy and early childhood, it frequently results in visual impairment. Congenital cataracts are phenotypically and genotypically heterogeneous and can occur in isolation or in association with other systemic disorders. Significant progress has been made in identifying the molecular genetic basis of cataract; 115 genes to date have been found to be associated with syndromic and non-syndromic cataract and 38 disease-causing genes have been identified to date to be associated with isolated cataract. In this review, we briefly discuss lens development and cataractogenesis, detail the variable cataract phenotypes and molecular mechanisms, including genotype-phenotype correlations, and explore future novel therapeutic avenues including cellular therapies and pharmacological treatments.
Cohen Syndrome-Associated Cataract Is Explained by VPS13B Functions in Lens Homeostasis and Is Modified by Additional Genetic Factors
AbstractPurpose: Cohen syndrome (CS) is a rare genetic disorder caused by variants of the VPS13B gene. CS patients are affected with a severe form of retinal dystrophy, and in several cases cataracts also develop. The purpose of this study was to investigate the mechanisms and risk factors for cataract in CS, as well as to report on cataract surgeries in CS patients. Methods: To understand how VPS13B is associated with visual impairments in CS, we generated the Vps13b∆Ex3/∆Ex3 mouse model. Mice from 1 to 3 months of age were followed by ophthalmoscopy and slit-lamp examinations. Phenotypes were investigated by histology, immunohistochemistry, and western blot. Literature analysis was performed to determine specific characteristic features of cataract in CS and to identify potential genotype-phenotype correlations. Results: Cataracts rapidly developed in 2-month-old knockout mice and were present in almost all lenses at 3 months. Eye fundi appeared normal until cataract development. Lens immunostaining revealed that cataract formation was associated with the appearance of large vacuoles in the cortical area, epithelial-mesenchymal transition, and fibrosis. In later stages, cataracts became hypermature, leading to profound retinal remodeling due to inflammatory events. Literature analysis showed that CS-related cataracts display specific features compared to other forms of retinitis pigmentosa-related cataracts, and their onset is modified by additional genetic factors. Corroboratively, we were able to isolate a subline of the Vps13b∆Ex3/∆Ex3 model with delayed cataract onset. Conclusions: VPS13B participates in lens homeostasis, and the CS-related cataract development dynamic is linked to additional genetic factors.
Expert Review of Ophthalmology · 2022 · 6 citations · open access
Evaluating gap junction variants for a role in pediatric cataract: an overview of the genetic landscape and clinical classification of variants in the <i>GJA3</i> and <i>GJA8</i> genes
AbstractIntroduction Variants in the two lens-expressed gap junction genes GJA3 and GJA8 are among the most common causes of inherited pediatric cataract. These two genes alone account for up to 18% of the cases, second only to the crystallin gene family.Areas covered All published cataract-associated variants in the GJA3 and GJA8 genes were reviewed for a role in pediatric cataract. Autosomal dominant inheritance was most frequently reported, alongside instances of reduced penetrance and autosomal recessive disease. Variant curation using the ACMG-AMP guidelines identified that many variants do not meet the modern standards for clinical interpretation of pathogenicity. There is broad phenotypic heterogeneity of cataract associated with gap junction gene variants. Pathogenic variants are located throughout both proteins with an enrichment in the N-terminal, first two transmembrane domains, and two extracellular loops.Expert opinion Nearly half the gap junction gene variants observed in cataract patients lack sufficient evidence of pathogenicity to form a useful clinical opinion. For many variants, this may be rectified over time as the variant is observed in additional patients but would be vastly accelerated by the generation of well-characterized and standardized functional data evaluating the specific effect of each variant on protein function.
International Journal of Ophthalmology · 2018 · 1 citations · open access
The J-shape association of serum total IgE levels with age-related cataract
AbstractAIM: To address the association between serum total IgE levels and age-related cataract in adults. METHODS: The study participants consisted of 1052 adults aged 40y or older in the Korean National Health and Nutrition Examination Survey 2010. We performed multivariable logistic regression analyses using the quartile cut-points of total IgE levels. RESULTS: The odds ratios (ORs) for nuclear and any cataract with ≥267 kU/L of serum IgE levels were 1.75 [95% confidence intervals (CI), 1.04-2.96] and 2.00 (95%CI, 1.22-3.27), respectively, comparing to 35-87 kU/L. Interestingly, participants with ≤35 kU/L of IgE levels (OR, 1.67; 95%CI, 1.02-2.72) also had higher risk for any cataract than those with 35-87 kU/L. The risk for any cataract (OR, 1.48; 95%CI, 1.03-2.13) was higher in participants with high total IgE levels (>150 kU/L), comparing to normal participants. CONCLUSION: Our findings indicate a J-shaped relationship between serum IgE levels and age-related cataract.
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.
