DeCure's autonomous Longevity AI scientist is researching a drug-repurposing hypothesis for age related macular degeneration 7 — screening already-approved drugs against its 5-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 7 maps to a 5-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 7 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
melanocortin 1 receptor (MC1R) — MC1R 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 7F4H · 2.7 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Age-related macular degeneration affects roughly one in three people by age 75 in developed countries, a 2006 commentary notes, but offers no trial data or treatment results. A 2010 rat study found that long-term intense cyclic light exposure caused progressive retinal degeneration: after one month, animals lost the outer segments of photoreceptors and about two-thirds of the outer nuclear layer, with subretinal pigment epithelium neovascularisation appearing. By three months, almost the entire outer nuclear layer was absent and choroidal neovascularisation had penetrated Bruch’s membrane into the outer retina. After six months, multiple foci of choroidal neovascularisation, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed. All exposed animals showed increased staining for 4-hydroxy-2-nonenal and nitrotyrosine, markers of oxidative damage. Optical coherence tomography and angiography confirmed retinal thinning and leaky new vessels.
A 2020 cell and mouse study tested lamivudine (3TC), a nucleoside analogue reverse transcriptase inhibitor, against Alu RNA-induced retinal pigment epithelium degeneration. In cultured human retinal pigment epithelium cells and in mouse retinal pigment epithelium in vivo, transfection with Alu RNA increased expression of the proinflammatory cytokines IL-18 and IL-1β. Treatment with 3TC markedly reduced that increase compared with a negative control. Alu RNA also induced expression of the senescence marker p16INK4a in human retinal pigment epithelium cells, and 3TC suppressed that induction. The authors conclude that Alu RNA accumulation contributes to retinal pigment epithelium senescence and that 3TC can suppress this process in the experimental system.
A 2015 review of genetic testing for age-related macular degeneration states that validated prediction models can estimate an individual’s likelihood of progression to advanced disease, and that including selected genotype data improves accuracy beyond phenotype alone in several studies. The review notes that identifying patients at increased genetic risk may alter monitoring strategies and physician recommendations, but it emphasises the limitations of testing, the need for additional data, and the requirement for appropriate patient selection, counselling, and education.
What is still missing: no human trial of lamivudine for age-related macular degeneration has been reported in these abstracts; the 2020 study is limited to cultured cells and mice. The rat model uses intense cyclic light in albino rats, which may not replicate human disease. Genetic testing remains an adjunct with no proven treatment benefit from genotype-directed therapy. No large, randomised, placebo-controlled trial in patients with geographic atrophy or neovascular age-related macular degeneration has been published for any repurposed drug in this set. Funding for such a trial, a design that accounts for the slow progression of the dry form, and reliable stratification of patients by genetic or molecular subtype are all absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2006 · 66 citations
A Very Effective Treatment for Neovascular Macular Degeneration
AbstractAge-related macular degeneration, a potentially blinding disease, is now epidemic in the developed world. Roughly one in three people will be affected to some degree by the age of 75 years.1 Medicine's tremendous successes in the battles against cancer, diabetes, hypertension, heart disease, and other common killers have raised the average life expectancy in many countries to more than 75 years and in so doing have inadvertently delivered a new scourge to mankind.In this issue of the Journal, de Jong2 discusses age-related macular degeneration as a complex disorder that begins decades before a patient becomes symptomatic, a molecular derangement . . .
Development of Choroidal Neovascularization in Rats With Advanced Intense Cyclic Light–Induced Retinal Degeneration
AbstractOBJECTIVES: To study the progressive changes of intense cyclic light-induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV). METHODS: Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by immunofluorescence staining. RESULTS: Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light-exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels. CONCLUSIONS: Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. CLINICAL RELEVANCE: The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.
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.
Expert Review of Ophthalmology · 2015 · 0 citations
Genetic testing for age-related macular degeneration: progress and perspectives
AbstractValidated prediction models estimate an individual’s likelihood of progression to advanced age-related macular degeneration. In several studies, inclusion of selected genotype improves accuracy beyond that achievable with phenotype alone. Identification of patients at increased genetic risk may provide opportunity to alter monitoring strategies and physician recommendations. Advancements in genetic testing can provide results that could refine and guide medical management and inform efforts to drive development and validation of genotype-directed therapies. Testing for age-related macular degeneration may be useful to physicians and select patients in specific clinical scenarios, and, as with all emerging diagnostic or therapeutic innovations, an awareness regarding the limitations of testing, the need for additional data, and need for appropriate patient selection, counseling and education are vital.
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.
