ArticleJCI insight2017
Therapeutic drug repositioning using personalized proteomics of liquid biopsies.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Artificial intelligence in ophthalmology: a bibliometric analysis of the 5-year trends in literature.Frontiers in medicine · 2025Pooled it
- Persistent Cytotoxic Immune Signaling in Anti-VEGF-Treated Neovascular Age-Related Macular Degeneration.medRxiv : the preprint server for health sciences · 2026Article
- Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) study protocol.BMJ open ophthalmology · 2025Article
- Treatment and Visual Outcomes in Pediatric Patients with Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy: A Cohort Study.Ocular immunology and inflammation · 2024Article
- Potential Prognostic Protein Biomarkers in Tears From Noninfectious Uveitis Patients Under Biologic Treatment as a Prelude to Personalized Medicine.Investigative ophthalmology & visual science · 2024Observational
- Genetic Linkage betweenInternational journal of molecular sciences · 2024Article
- Liquid Biopsy Proteomics in Ophthalmology.Journal of proteome research · 2024Review
- Intraoperative Complications With Vitreous Biopsy for Molecular Proteomics.Ophthalmic surgery, lasers & imaging retina · 2023Article
- Long-Term Outcomes and Risk Factors for Severe Vision Loss in Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV).American journal of ophthalmology · 2022Observational
- Review
- Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach.International journal of molecular sciences · 2021Article
- Molecular Surgery: Proteomics of a Rare Genetic Disease Gives Insight into Common Causes of Blindness.iScience · 2020Review
- Phenotypic variance in Calpain-5 retinal degeneration.American journal of ophthalmology case reports · 2020Article
- Structural Insights into the Unique Activation Mechanisms of a Non-classical Calpain and Its Disease-Causing Variants.Cell reports · 2020Article
- Protein Biomarkers in Uveitis.Frontiers in immunology · 2020Review
- CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials.Human mutation · 2019Article
- Nanotechnology in regenerative ophthalmology.Advanced drug delivery reviews · 2019Review
- Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy.Scientific reports · 2019Article
- Early Onset Neovascular Inflammatory Vitreoretinopathy Due to aOcular immunology and inflammation · 2019Article
- Personalized Proteomics for Precision Health: Identifying Biomarkers of Vitreoretinal Disease.Translational vision science & technology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIn patients with limited response to conventional therapeutics, repositioning of already approved drugs can bring new, more effective options. Current drug repositioning methods, however, frequently rely on retrospective computational analyses and genetic testing - time consuming methods that delay application of repositioned drugs. Here, we show how proteomic analysis of liquid biopsies successfully guided treatment of neovascular inflammatory vitreoretinopathy (NIV), an inherited autoinflammatory disease with otherwise poor clinical outcomes.
methodsVitreous biopsies from NIV patients were profiled by an antibody array for expression of 200 cytokine-signaling proteins. Non-NIV controls were compared with NIV samples from various stages of disease progression. Patterns were identified by 1-way ANOVA, hierarchical clustering, and pathway analysis. Subjects treated with repositioned therapies were followed longitudinally.
resultsProteomic profiles revealed molecular pathways in NIV pathologies and implicated superior and inferior targets for therapy. Anti-VEGF injections resolved vitreous hemorrhages without the need for vitrectomy surgery. Methotrexate injections reversed inflammatory cell reactions without the side effects of corticosteroids. Anti-IL-6 therapy prevented recurrent fibrosis and retinal detachment where all prior antiinflammatory interventions had failed. The cytokine array also showed that TNF-α levels were normal and that corticosteroid-sensitive pathways were absent in fibrotic NIV, helping explain prior failure of these conventional therapeutic approaches.
conclusionsPersonalized proteomics can uncover highly personalized therapies for autoinflammatory disease that can be timed with specific pathologic activities. This precision medicine strategy can also help prevent delivery of ineffective drugs. Importantly, proteomic profiling of liquid biopsies offers an endpoint analysis that can directly guide treatment using available drugs.
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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.