ArticleNature medicine2024
Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results.
Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04537884 (A Phase 1, Open-Label, Single Ascending Dose Study to Assess the Safety and Tolerability of a Single Intravitreal Injection of UBX1325 in Patients With Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration), which is not on this map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1, Open-Label, Single Ascending Dose Study to Assess the Safety and Tolerability of a Single Intravitreal Injection of UBX1325 in Patients With Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- [Liquid biopsy proteomics in ophthalmology : A clinical and scientific perspective].Die Ophthalmologie · 2026Pooled it
- Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.Nature medicine · 2024Trial
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- A compendium of circulating biomarkers of senescence in humans: Insights on mechanistic impact across health domains and modulation by therapeutic interventions.Ageing research reviews · 2026Review
- A Mechanism-Based Framework for Anti-Aging Strategies: From Metabolic Regulation to Senotherapy and Stem Cell-Based Interventions.Aging cell · 2026Review
- Fibrillarin Resists Cellular Senescence Via SIRT1-Dependent Nicotinamide Metabolism and Its Inhibition Sensitizes Senolytic Therapy in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microglial checkpoint collapse in Alzheimer's disease: a tri-axial framework for biomarker-informed neuroimmune therapy.Journal of neuroinflammation · 2026Review
- The role and potential therapeutic intervention of cellular senescence in intervertebral disc degeneration.Genes & diseases · 2026Review
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Review
- Proteomic clocks combined with deep learning phenotypes track eye aging and diseases.NPJ digital medicine · 2026Article
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Cellular senescence as a therapeutic target for aging intervention.Biomedical journal · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Single-cell insights into maladaptive endothelial plasticity and therapeutic targets in diabetic vascular complications.Cardiovascular diabetology · 2026Review
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
- Bst2-targeted senotherapy restores visual function by eliminating senescent retinal cells.Nature communications · 2026Article
- Dual-Target ROS-Driven Spatiotemporal Senolysis for Vascular Repair and Immune Microenvironment Reprogramming in the Treatment of Ocular Fundus Neovascularization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 3 institutions in 2 countries.
Funding
Abstract
Compromised vascular endothelial barrier function is a salient feature of diabetic complications such as sight-threatening diabetic macular edema (DME). Current standards of care for DME manage aspects of the disease, but require frequent intravitreal administration and are poorly effective in large subsets of patients. Here we provide evidence that an elevated burden of senescent cells in the retina triggers cardinal features of DME pathology and conduct an initial test of senolytic therapy in patients with DME. In cell culture models, sustained hyperglycemia provoked cellular senescence in subsets of vascular endothelial cells displaying perturbed transendothelial junctions associated with poor barrier function and leading to micro-inflammation. Pharmacological elimination of senescent cells in a mouse model of DME reduces diabetes-induced retinal vascular leakage and preserves retinal function. We then conducted a phase 1 single ascending dose safety study of UBX1325 (foselutoclax), a senolytic small-molecule inhibitor of BCL-xL, in patients with advanced DME for whom anti-vascular endothelial growth factor therapy was no longer considered beneficial. The primary objective of assessment of safety and tolerability of UBX1325 was achieved. Collectively, our data suggest that therapeutic targeting of senescent cells in the diabetic retina with a BCL-xL inhibitor may provide a long-lasting, disease-modifying intervention for DME. This hypothesis will need to be verified in larger clinical trials. ClinicalTrials.gov identifier: NCT04537884 .
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.