DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cataract 5 multiple types — 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 moduleCataract 5 multiple types 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 cataract 5 multiple types 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
heat shock transcription factor 4 (HSF4) — HSF4 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 6J6V · 1.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a four-generation Chinese family with congenital nuclear pulverulent and posterior polar cataracts, a heterozygous c.5G>A transition in GJA3 was identified, substituting glycine with aspartic acid at the N-terminus of connexin46. When expressed in HeLa cells, the mutant Cx46G2D formed gap junction plaques inefficiently, changed hemichannel permeability, and caused apoptosis. The glycine residue at the second position of the N-terminus appears important for gap junction plaque formation and hemichannel function. No treatment was tested in this study.
A 2023 genome-wide association study of age-related cataracts used 127,985 cases and 837,371 controls and identified 85 independent genome-wide significant loci, 37 of which were novel. Gene-based association tests found 126 genes associated with cataracts, hinting at a potential relationship between negative regulation of lipid biosynthesis and cataract development. Four of the genes — GNL3, JAG1, METTL21A, and CREB1 — are involved in drug-gene interactions, from which drug repurposing could be proposed. Mendelian randomisation analysis identified a putative causal relationship between genetic predisposition to type 1 diabetes and an increased risk of cataracts. Evidence also indicated that early-life exposure to ultraviolet radiation may impact later cataract development.
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 review discusses future therapeutic avenues including cellular therapies and pharmacological treatments, but provides no trial data, no survival or response rates, and no evidence that any drug has been tested in patients for cataract.
No drug has been shown in these abstracts to prevent, slow, or reverse any form of cataract in humans. What is missing is any clinical trial of a repurposed drug for cataract, any patient stratification strategy, and the funding to move from genetic association and in vitro findings to human testing.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Ophthalmology · 2020 · 85 citations · open access
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.
A novel<i>GJA3</i>mutation associated with congenital nuclear pulverulent and posterior polar cataract in a chinese family
AbstractCongenital cataract (CC) is the leading cause of visual disability in children. To date, mutations in many genes have been linked to CC. In a four-generation Chinese family with congenital nuclear pulverulent and posterior polar cataracts, we detected a heterozygous c.5G>A transition in the second exon of GJA3, resulting in the substitution of a highly conserved glycine with aspartic acid (p.G2D) at the N-terminus of the connexin46 (Cx46) protein. Wild type (wt) and mutant Cx46 plasmids were transfected into HeLa cells to examine the molecular basis of cataract formation. Unlike wt Cx46, Cx46G2D mutant formed gap junction plaques inefficiently, changed hemichannel permeability, and caused apoptosis. These results suggest that the glycine residue at the second position of the N-terminus is important for gap junction plaque formation and hemichannel function.
Dolasetron, Droperidol und die Kombination beider Substanzen zur Prophylaxe von Übelkeit und Erbrechen nach extrakapsulären Kataraktextraktionen in Allgemeinanästhesie
AbstractBACKGROUND: Both, droperidol and the new 5-HT3-antagonist (e.g. dolasetron) are effective drugs in the prevention of postoperative nausea and vomiting (PONV). It was the aim of this prospective double blind placebo controlled study to determine the efficacy of low-dose droperidol, dolasetron, and a combination of both drugs in the prevention of PONV after extracapsular cataract extraction. METHODS: 148 inpatients undergoing cataract surgery were stratified according to gender and then randomised to receive one of four antiemetic regimens: placebo, droperiodol (10 micrograms x kg-1), dolasetron (12.5 mg), or the combination of both drugs (10 micrograms x kg-1 + 12.5 mg). The drugs were administered intravenously 5-10 minutes before the end of anaesthesia. General anaesthesia and the perioperative management of the patients were standardised: benzodiazepine premedication, induction with etomidate, alfentanil and mivacurium. Maintenance using desflurane in N2O/O2, and a continuous infusion of mivacurium was used. Postoperative analgesia (diclofenac or paracetamol) and antiemetic rescue medication (dimenhydrinate and metoclopramide) was standardised. Nausea, episodes of vomiting, retching and the need for additional antiemetics were recorded for 24-hours. The severity of PONV was categorised using a standardised scoring algorithm. The main aim of the study was the number of patients who stayed completely free from PONV. RESULTS: There were no differences between the two groups with regard to biometric data, type of surgery, and distribution of risk factors for developing PONV. In all three treatment groups significantly less patients suffered from PONV (placebo: 66%; droperidol: 89%, dolasetron: 92%, combination: 89%; p = 0.011). Furthermore, the severity of PONV was reduced (p = 0.012). CONCLUSION: Low-dose droperidol and dolasetron are equally effective to reduce the incidence of PONV after cataract surgery under general anaesthesia. The combination of both drugs revealed no additional effect.
Research Square · 2023 · 0 citations · open access
Uncovering Novel Genetic Loci and Biological Pathways Associated with Age-Related Cataracts through GWAS Meta-Analysis
AbstractAbstract Background Age-related cataract is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation (UVR), and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear. Further research into the genetic basis of cataracts could provide valuable insights into the disease's etiology and lead to a better understanding of biological mechanisms that are associated with its development. Methods This study presents the largest genome-wide association study of cataracts to date, using data from 127,985 cases and 837,371 controls. We performed gene enrichment analysis to identify genes and biological pathways associated with cataracts. We integrated our results with gene expression reference datasets to identify genetic variants modifying risk for cataracts through changes in the expression of specific genes. We further explored drug-gene interactions to better understand the potential impact of pharmacological interventions on cataract development. Finally, we explored whether a causal relationship underlies the known comorbidity between type 1 diabetes and cataracts using a mendelian randomization framework, and the association between UV exposure and cataract risk in adults using a polygenic risk scoring approach. Findings Our study identified 85 independent genome-wide significant loci, 37 of which are novel. Gene-based association tests identified 126 genes associated with cataracts, hinting at a potential relationship between negative regulation of lipid biosynthesis and the development of cataracts. Four of the genes identified GNL3 , JAG1 , METTL21A , and CREB1 are involved in drug-gene interactions. Moreover, Mendelian Randomisation analysis identified a putative causal relationship between genetic predisposition to type 1 diabetes and an increased risk of cataracts. Lastly, we found evidence indicating that early-life exposure to UVR may have an impact on the later development of cataracts. Interpretation Our findings advance our understanding of the genetic basis of cataract and provide new insights into its etiology. We identified multiple genes and biological pathways associated with the condition, including associations with four genes from which drug repurposing could be proposed. Our results suggest a causal association between type 1 diabetes and cataracts. Also, we highlighted a surrogate measure of UV light exposure as a marker of cataract risk in adults and drug-genes interactions that has the potential of informing novel therapies.
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.
