DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for late-onset retinal degeneration — 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 moduleLate-onset retinal degeneration 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
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside late-onset retinal degeneration in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
What the evidence adds up to
In a 2013 study of two closely related terrier breeds, early-onset retinal degenerations were linked to mutations in PDE6B (a three-base deletion in exon 21) and IQCB1 (a cytosine insertion in exon 10). Affected dogs showed abnormal rod and cone inner and outer segments from as young as three weeks (crd2) or eleven weeks (crd1), progressing to severe outer segment loss and thinning of the outer nuclear layer by twelve weeks. The authors proposed these dogs as large animal models for homologous human diseases, but no human trial or therapeutic application was reported.
A 2023 post hoc analysis of the PREVENT trial tested prophylactic ranibizumab injections every three months in eyes with intermediate age-related macular degeneration. Over 24 months, there were no statistical differences between the ranibizumab and sham groups in drusen volume, macular thinning, or geographic atrophy growth rate. Among the nine eyes with geographic atrophy, mean growth was 1.34 mm²/year with ranibizumab versus 1.95 mm²/year with sham (p=0.49), and square root transformation also showed no significant difference (p=0.61). The drug did not appear to affect progressive retinal degeneration in this setting.
A 2007 review discussed non-cell-autonomous mechanisms and signalling cascades in retinal degeneration, suggesting they might serve as therapeutic targets, but offered no clinical data. A 2010 review of peripheral retinal degenerations described which lesions predispose to retinal detachment and might warrant prophylactic treatment, but it did not address late-onset retinal degeneration specifically.
What is still missing: no clinical trial has tested any drug specifically for late-onset retinal degeneration in humans; the animal model work has not been translated into a funded human study; patient stratification by genetic subtype has not been attempted; and no trial design has been proposed that accounts for the slow, variable progression of late-onset disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
<i>IQCB1</i>and<i>PDE6B</i>Mutations Cause Similar Early Onset Retinal Degenerations in Two Closely Related Terrier Dog Breeds
AbstractPURPOSE: To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively. METHODS: Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the "MAGIC" genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease. RESULTS: Structural photoreceptor abnormalities were observed in crd1-affected dogs as young as 11-weeks old. Rod and cone inner segment (IS) and outer segments (OS) were abnormal in size, shape, and number. In crd2-affected dogs, rod and cone IS and OS were abnormal as early as 3 weeks of age, progressing with age to severe loss of the OS, and thinning of the outer nuclear layer (ONL) by 12 weeks of age. Genome-wide association study (GWAS) identified association at the telomeric end of CFA3 in crd1-affected dogs and on CFA33 in crd2-affected dogs. Candidate gene evaluation identified a three bases deletion in exon 21 of PDE6B in crd1-affected dogs, and a cytosine insertion in exon 10 of IQCB1 in crd2-affected dogs. CONCLUSIONS: Identification of the mutations responsible for these two early-onset retinal degenerations provides new large animal models for comparative disease studies and evaluation of potential therapeutic approaches for the homologous human diseases.
Retinal Degenerations: From Cell Signaling to Cell Therapy; Pre-Clinical and Clinical Issues
AbstractExtracellular signaling molecules have been implicated in the progression of Retinal Degeneration (RD). Gene regulatory events linked to the maintenance of retinal structure and function incorporate signaling cascades that may serve as therapeutic targets for some forms of blindness. This review shall focus on the evidence for non-cell-autonomous mechanisms that affect the pattern of degeneration seen in retinal dystrophies, the types of signals that may influence the course of degeneration and finally with the related prospects for retinal-therapies.
Impact of Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration on Eyes With Intermediate Age-Related Macular Degeneration
AbstractPurpose: The purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial. Methods: This post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24 months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed. Results: There were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24 months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9 eyes with GA in this study, mean GA growth rate from baseline to 24 months was 1.34 +/- 0.79 mm2/year after PR and 1.95 +/- 1.73 mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61). Conclusions: Prophylactic ranibizumab given every 3 months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD. Translational Relevance: This work investigates the impact of PR on progressive retinal degeneration in a clinical trial.
Efficacy of 190 mcg fluocinolone acetonide intravitreal implant: microperimetry and OCT real-life data.
AbstractOBJECTIVE: Fluocinolone acetonide is a valid alternative treatment for patients with chronic diabetic macular edema (DME) with poor response to anti-vascular endothelial growth factor (VEGF) therapy. The purpose of this study is to report the efficacy and safety of ILUVIEN® implant in pseudophakic eyes with persistent DME. PATIENTS AND METHODS: This is a single-centre pilot-study of 8 patients with persistent DME treated with the ILUVIEN implant, despite previous anti-vascular endothelial growth factor and/or steroid treatment. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) central retinal thickness, intraocular pressure (IOP) and microperimetric data were evaluated at baseline and month 1, 3 and 6 post treatment. RESULTS: All data are presented as mean and standard deviation. At baseline, 1, 3 and 6 months, we had BCVA of 0.26±0.22, 0.38±0.27, 0.48±0.27 and 0.46±0.24; IOP of 15.00±2.67, 15.50±3.16, 14.88±2.42 and 15.63±2.67 mmHg; macular thickness of 652±231, 487±278, 475±287 and 413±211 µm; macular sensitivity of 6.83±4.20, 6.13±3.72, 7.68±3.40 and 7.71±3.33 dB; bivariate contour elliptic area (BCEA) 95.4% 3.8±3.42, 6.06±10.06, 3.05±2.46 and 2.59±2.19°2. CONCLUSIONS: According to the results of our study, fluocinolone acetonide (FAc) is a valid therapy option despite some limitations. It has been evidenced that FAc is more effective in patients with mild central macular thickening, while in those with modest to severe central macular thickness (CMT), different therapy strategies should be considered.
Delhi Journal of Ophthalmology · 2010 · 0 citations · open access
Peripheral Retinal Degenerations
AbstractThe vast array of peripheral retinal degenerations leave an ophthalmologist with numerous possible differentials and prognosticators when an individual presents to him. The following review is an aid in understanding which degenerations make retina susceptible to a possible retinal detachment in near future; and are possible indicators for prophylactic therapy at presentation and which of them do not predispose to any complications and thus can be left untreated.
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.
