DeCure's autonomous Longevity AI scientist is researching a drug-repurposing hypothesis for age-related macular degeneration — screening already-approved drugs against its 36-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAge-related macular degeneration maps to a 36-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 age-related macular degeneration 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
synapsin III (SYN3) — SYN3 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2P0A · 1.9 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
Lamivudine (3TC) reduced Alu RNA-induced expression of the proinflammatory cytokines IL-18 and IL-1β in cultured human retinal pigment epithelium (RPE) cells and in mouse RPE cells in vivo, compared with a negative control. Alu RNA-induced expression of the senescence marker p16INK4a was also suppressed by 3TC in human RPE cells. These experiments used cells transfected with in vitro-transcribed Alu RNA, not tissue from patients with age-related macular degeneration. The study did not measure any clinical outcome such as visual acuity, lesion size, or progression to geographic atrophy.
A 2007 review notes that before photodynamic therapy and anti-vascular endothelial growth factor agents, the only treatment for neovascular age-related macular degeneration was laser photocoagulation, which could stabilise vision but was not enthusiastically received. Anti-VEGF drugs then allowed better visual outcomes than mere stabilisation. The same review states there is still no cure for the disease. A 2021 overview repeats that current treatments only delay loss of central vision and that more efficient treatments are needed.
No clinical trial of lamivudine in patients with age-related macular degeneration has been reported. The 2020 cell and mouse study did not test whether lamivudine reaches the human retina at therapeutic concentrations, nor did it examine effects on choroidal neovascularisation, the hallmark of the wet form of the disease. What is missing is a clinical trial with a sufficient sample size, a clear endpoint such as change in geographic atrophy area or visual acuity, and stratification by disease stage and genotype. Funding for such a trial has not been described.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Retina · 2012 · 65 citations
CURRENT KNOWLEDGE AND TRENDS IN AGE-RELATED MACULAR DEGENERATION
AbstractPURPOSE: To address the most dynamic and current issues concerning today's treatment options and promising research efforts regarding treatment for age-related macular degeneration. This review is aimed to serve as a practical reference for more in-depth reviews on the subject. METHODS: An online review of the database PubMed and Ovid were performed, searching for the key words age-related macular degeneration, AMD, VEGF, treatment, PDT, steroids, bevacizumab, ranibizumab, VEGF-trap, radiation, combined therapy, as well as their compound phrases. The search was limited to articles published since 1985. All returned articles were carefully screened, and their references were manually reviewed for additional relevant data. The web page www.clinicaltrials.gov was also accessed in search of relevant research trials. RESULTS: A total of 363 articles were reviewed, including 64 additional articles extracted from the references. At the end, only 160 references were included in this review. CONCLUSION: Treatment for age-related macular degeneration is a very dynamic research field. While current treatments are mainly aimed at blocking vascular endothelial growth factor, future treatments seek to prevent vision loss because of scarring. Promising efforts have been made to address the dry form of the disease, which has lacked effective treatment.
Lamivudine Inhibits<i>Alu</i>RNA-induced Retinal Pigment Epithelium Degeneration via Anti-inflammatory and Anti-senescence Activities
AbstractPurpose: Accumulation of the long noncoding Alu element RNA activates the NLRP3 inflammasome and leads to retinal pigment epithelium (RPE) cell death, a key event in the pathogenesis of geographic atrophy during late-stage age-related macular degeneration. Lamivudine (3TC) is a nucleoside analog reverse transcriptase inhibitor known to inhibit the NLRP3 inflammasome. Currently, the intracellular response of the senescence marker p16Ink4a to the long noncoding RNA is being actively studied. The present study aimed to assess the efficacy of 3TC against Alu RNA-induced RPE inflammation and senescence by evaluating changes in expression of the proinflammatory cytokines IL-18 and IL-1β and of p16INK4a in RPE cells. Methods: Cultured human RPE cells and in vivo mouse RPE cells were transfected with an in vitro-transcribed Alu RNA, and changes in IL-18, IL-1β, and p16Ink4a expression measured in the presences of 3TC or 3,4-(M)CA as a negative control. Results: Treatment with 3TC markedly reduced Alu RNA-induced expression of IL-18 and IL-1β in human and mouse RPE cells compared with the negative control. Further, Alu RNA-induced p16INK4a expression was suppressed by 3TC in human RPE cells. Conclusions: Our data suggest that Alu RNA accumulation contributes to RPE cell senescence in age-related macular degeneration and that this pathogenic process can be suppressed by 3TC. Translational Relevance: Further verifying this study leads to potential targets for age-related macular degeneration therapy.
Current Opinion in Ophthalmology · 2007 · 9 citations
Treatment of neovascular age-related macular degeneration: past, present and future directions
AbstractPURPOSE OF REVIEW: The treatment options of choroidal neovascularization due to age-related macular degeneration have expanded. Prior to ocular photodynamic therapy the only available treatment was laser photocoagulation. Clinicians and patients were not particularly enthusiastic despite its ability to stabilize vision. The purpose of the review is to review the past and current concepts of neovascular age-related macular degeneration therapy and to provide a short overview of upcoming treatments. RECENT FINDINGS: Photodynamic therapy provided us with the first realistic means to address subfoveal choroidal neovascularization lesions from age-related macular degeneration. Antivascular endothelial growth factors now allow better visual outcomes than mere stabilization of vision and other promising treatments are undergoing study at this time. SUMMARY: Age-related macular degeneration therapy has undergone a significant revolution in recent years. Understanding the historical perspective of treatment provides a better appreciation of current therapies. Still there is no cure for this disease and more promising treatments are currently under investigation.
Revista Brasileira de Oftalmologia · 2021 · 2 citations · open access
Age-related macular degeneration: an overview
AbstractAge-related macular degeneration is the most important cause of irreversible vision loss in the elderly and has been considered a severe public health problem. Current treatments have only been successful in delaying the loss of central vision. Due to increased life expectancy, governments and researchers have been challenged to seek more efficient and successful treatments for age-related macular degeneration. Considering its relevance for public health and the need of further research, this article aims to address age-related macular degeneration objectively, tackling on the current knowledge about its pathophysiology, potential molecular biomarkers, main prevention procedures and treatments, as well as introducing possible molecules that may be a therapeutic target in this disease.
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.
