DeCure's autonomous Longevity AI scientist is researching a drug-repurposing hypothesis for age related macular degeneration 11 — 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 moduleAge related macular degeneration 11 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 age related macular degeneration 11 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
cystatin C (CST3) — CST3 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 3GAX · 1.7 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
One 2020 laboratory study tested lamivudine (3TC) in cultured human retinal pigment epithelium cells and in mouse RPE cells. Cells were transfected with Alu RNA to mimic the inflammation and senescence seen in geographic atrophy, the late-stage dry form of age-related macular degeneration. Lamivudine treatment markedly reduced the Alu RNA-induced expression of the proinflammatory cytokines IL-18 and IL-1β in both human and mouse cells compared with a negative control. It also suppressed the Alu RNA-induced expression of the senescence marker p16INK4a in human RPE cells. The authors concluded that Alu RNA accumulation contributes to RPE cell senescence and that this pathogenic process can be suppressed by lamivudine. No human data, no dosing information, and no survival or visual acuity outcomes were reported.
A 2017 review of prevention strategies for age-related macular degeneration noted that available therapeutic options are limited. It stated that the Age-Related Eye Disease Studies 1 and 2 showed a beneficial role of antioxidants in a selected group of patients. The review did not report any new drug efficacy data or clinical trial results for any specific compound.
A 2007 review of treatment for neovascular (wet) age-related macular degeneration described the historical shift from laser photocoagulation to photodynamic therapy and then to anti-vascular endothelial growth factor agents. It stated that anti-VEGF drugs allowed better visual outcomes than mere stabilisation of vision. The review also noted that there was still no cure for the disease and that more promising treatments were under investigation. No new drug efficacy numbers or trial results were presented.
What is still missing is any human clinical trial of lamivudine for age-related macular degeneration, whether dry or wet. The laboratory evidence is limited to cell culture and mouse models. No dosing, safety, or visual outcome data exist for patients. No trial design, funding, or patient stratification strategy has been reported for this repurposing approach.
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 · 2013 · 136 citations
CURRENT KNOWLEDGE AND TRENDS IN AGE-RELATED MACULAR DEGENERATION
AbstractPURPOSE: To address the most dynamic and current issues concerning human genetics, risk factors, pharmacoeconomics, and prevention regarding age-related macular degeneration. METHODS: An online review of the database Pubmed and Ovid was performed, searching for the key words: age-related macular degeneration, AMD, pharmacoeconomics, risk factors, VEGF, prevention, genetics and their compound phrases. The search was limited to articles published since 1985 to date. All returned articles were carefully screened and their references were manually reviewed for additional relevant data. The webpage www.clinicaltrials.gov was also accessed in search of relevant research trials. RESULTS: A total of 366 articles were reviewed, including 64 additional articles extracted from the references and 25 webpages and online databases from different institutions. At the end, only 244 references were included in this review. CONCLUSION: Age-related macular degeneration is a complex multifactorial disease that has an uneven manifestation around the world but with one common denominator, it is increasing and spreading. The economic burden that this disease poses in developed nations will increase in the coming years. Effective preventive therapies need to be developed in the near future.
ISRN Ophthalmology · 2014 · 28 citations · open access
Present and Possible Therapies for Age-Related Macular Degeneration
AbstractAge-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment options for this condition remain substantially limited. In this review, we outline the existing arsenal of therapies available for AMD and discuss the additional role of further novel therapies currently under investigation for this debilitating disease.
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.
Asia-Pacific Journal of Ophthalmology · 2017 · 15 citations
Prevention of Age-Related Macular Degeneration
AbstractAge-related macular degeneration (AMD) compromises quality of life. However, the available therapeutic options are limited. This has led to the identification of modifiable risk factors to prevent the development or alter the natural course and prognosis of AMD. The identification and modification of risk factors has the potential for greater public health impact on reducing morbidity from AMD. Likewise, identifying the imaging clues and genetic clues could serve as a guide to recognizing the propensity for progression to severe and end stages of the disease. Several attempts, both successful and unsuccessful, have been made for interventions that could delay the progression of AMD. Of these, pharmacological interventions have shown promising results. The Age-Related Eye Disease Study 1 and 2 have shown the beneficial role of antioxidants in a selected group of patients.
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.
Wiadomości Lekarskie · 2021 · 1 citations · open access
AGE-RELATED MACULAR DEGENERATION – CURRENT STATE OF THE PROBLEM AND PROPHYLAXIS METHODS
AbstractOBJECTIVE: The aim: Analyze the ophthalmic studies on diagnostics and treatment of patients with age-related macular degeneration to optimize diagnostics and management tactics. PATIENTS AND METHODS: Materials and methods: The analysis of scientific papers due to age-related macular degeneration, vitamin D and its functions from scientometric databases: PubMed, Scopus, Web of Science. The methods were next: systematic approach, analysis, summarization and comparison. CONCLUSION: Conclusions: Age-related macular degeneration is a chronic, progressive disease among people older than 50 years. Late diagnostics and inappropriate treatment may lead to irreversible central vision loss and social disadaptation. Modern studies on the pathogenesis and treatment of this pathology (that are due to the role of the immune system, antioxidants and microelements) demonstrate the effectiveness and prospects for further development around the world to find new ways to solve this problem.
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.
