SBIR-STTR Award

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 60 in the developed world. Progression of this disease results in the loss of the ability to perform activities highly correlated with quality of life. The disease process is not well understood. Treatments address only portions of the underlying mechanisms of the disease and there is no cure. The current standard of care is repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) pharmacologic treatment. However, only 34%-40% of patients gain clinically significant vision and maintain that gain over the course of one to two years. Currently non-responders are identified only after months of ineffective treatment. Our objective is to validate a panel of biomarkers that predict clinical non-responders to anti-VEGF monotherapy so that physicians can quickly identify patients who would benefit from alternative therapy rather than waiting for months to clinically demonstrate treatment failure before implementing these other therapeutic strategies. We have discovered the presence of cell receptors and their activated phosphorylated forms in the vitreous fluid of human eyes and that there are significant protein level differences between anti-VEGF treatment responders and non-responders. Ocular Proteomics, LLC (OPL)'s approach will be based on the use of reverse-phase protein microarray (RPPM) technology to accurately discriminate different disease states in at-risk patients. OPL is at the forefront of a small group that uses RPPM technology to investigate biomarkers for degenerative ocular diseases. Results will lead the way for this project to study the predictive potential of the vitreous proteome for retinal diseases, including wet AMD. Hypotheses 1) The baseline proteome of wet AMD patients is distinctive from that of healthy normals or patients with other types of eye diseases. 2) The baseline vitreous proteome of wet AMD non-responders to anti-VEGF therapy differs significantly from that of wet AMD responders. 3) Differences in the baseline proteome of responders and non-responders are likely to lie in proteins involved in the VEGF, angiogenesis, and/or inflammatory pathways. The Specific Aims of the proposal are: (Aim 1) use model of clinical response to form cohorts of vitreous samples for biomarker analysis, (Aim 2) profile candidate vitreous biomarkers using antibody microarrays, and (Aim 3) validate and quantify the biomarkers. , ,

Public Health Relevance:
The proposed research will improve public health by improving the vision of patients with wet age-related macular degeneration at reduced costs. It will do this by producing a product that will allow retina physicians to perform a test that will determine how a patient will respond to a given treatment before starting the patient on this treatment. This will allow the doctor to choose the right treatment for the right patient at the right time, providing truly personalized medicine.

Thesaurus Terms:
Address;Age;Age Related Macular Degeneration;Alternative Therapies;Anti-Inflammatories;Anti-Inflammatory Agents;Antibodies;Antiinflammatories;Antiinflammatory Agents;Blindness;Chronic;Clinical;Clinical Trials;Clinical Trials, Unspecified;Control Groups;Degenerative Disorder;Deterioration;Development;Diagnostic;Diagnostic Tests;Disease;Disease Management;Disease Progression;Disorder;Disorder Management;Doppler Oct;Drugs;Eye;Eye Diseases;Eyeball;F And A;Facilities And Administrative Costs;Facilities And Administrative Costs (F And A);Group Identifications;Human;Human, General;Indirect Costs;Individual;Inflammatory;Lead;Libraries;Liquid Substance;Maculopathy, Age-Related;Man (Taxonomy);Man, Modern;Medication;Medicine;Microarray Analysis;Microarray-Based Analysis;Modeling;Oct Tomography;Optical Coherence Tomography;Pathway Interactions;Patient Rights;Patients;Pb Element;Pharmaceutic Preparations;Pharmaceutical Preparations;Phase;Physicians;Process;Protein Biochips;Protein Chips;Protein Microarray;Protein Microchips;Proteins;Proteome;Proteomics;Public Health;Qol;Quality Of Life;Receptor Cell;Research;Retina;Retinal Diseases;Retinal Disorder;Retinal Vein Occlusion;Risk;Sampling;Sampling Studies;Science Of Medicine;Sight;Testing;Therapeutic;Time;Tomography, Optical Coherence;Treatment Failure;Vegfs;Validation;Vascular Endothelial Growth Factors;Vegf;Vision;Visual;Visual Acuity;Angiogenesis;Base;Biomarker;Clinical Investigation;Clinical Significance;Clinically Significant;Cohort;Commercialization;Cost;Degenerative Condition;Degenerative Disease;Diabetic;Disease/Disorder;Drug/Agent;Experiment;Experimental Research;Experimental Study;Eye Disorder;Fluid;Gene Product;Heavy Metal Pb;Heavy Metal Lead;Improved;Innovate;Innovation;Innovative;Liquid;Macular Edema;Microarray Technology;New Approaches;Novel Approaches;Novel Strategies;Novel Strategy;Ophthalmopathy;Pathway;Prospective;Public Health Medicine (Field);Public Health Relevance;Research Study;Response;Retina Disease;Retina Disorder;Retinopathy;Senile Macular Disease;Standard Of Care;Tool

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 60 in the developed world. Progression of this disease results in the loss of the ability to perform activities highly correlaed with quality of life. This disease progression is not well understood and treatments address only portions of the underlying mechanisms of the disease, while there is no cure. The current standard of care is repetitive intravitreal anti-vascular endothelial growth factor (anti-VEGF) pharmacologic treatment. However, only 34-40% of patients gain clinically significant vision and maintain that gain over the course of one to two years. Ocular Proteomics, LLC (OPL)'s objective is to validate a panel of biomarkers that predict clinical non-responders to anti-VEGF therapy to allow physicians to quickly identify those who would benefit from alternative therapies. The current methodology is the alternative, where non-responders are identified only after months of ineffective treatment. The OPL lab previously discovered the presence of cell receptors and their phosphorylated (activated) forms in the vitreous fluid of human eyes. Significant quantitative differences in several proteins between anti-VEGF treatment responders and non-responders were demonstrated. OPL's approach has been centered on the use of R.P.P.M. (reverse-phase protein microarray) technology to accurately discriminate different disease states in patients. Also, recent discoveries show quantitative differences between subsets of patients within some small disease groups. The next phase is to employ these past discoveries to uncover additional differences between responsive and non-responsive patients. Long term objectives include validating these unique quantitative differences among larger populations, as well as disseminating the molecular mechanisms of disease progression. The results achieved from these objectives will lead to predicting response retinal diseases, including wet AMD using the Diagnostic Vitreous Proteome. The specific aims of this proposal include: 1) Recruit patients with wet AMD from multiple retina centers across the country to participate in the study 2) Validate Efficacy of potential Biomarkers to Predict Treatment Response and Disease Progression 3) Finalize most significant AMD biomarkers for determining and predicting Treatment Response and Disease Progression

Public Health Relevance Statement:


Public Health Relevance:
The proposed research will improve public health by improving the vision of patients with wet age-related macular degeneration at reduced costs. It will do this by producing a product that will allow retina physicians to perform a diagnostic test that will determine how a patient will respond to a given treatment before starting the patient on this treatment. This will allow the doctor to choose the right treatment for the right patient at te right time, providing truly personalized medicine.

Project Terms:
Address; Affect; Age; Age related macular degeneration; Alternative Therapies; Ants; Aspirate substance; assay development; base; Bioinformatics; Biological; Biological Markers; Biological Process; Blindness; Clinical; Clinical Data; Clinical Trials; clinically significant; Collaborations; commercialization; cost; Country; Data; Development; Diabetic Retinopathy; Diagnostic; Diagnostic tests; Disease; Disease Progression; Early Diagnosis; Early treatment; Economic Burden; Ensure; Enzyme-Linked Immunosorbent Assay; Eye; FDA approved; Funding; Glaucoma; Goals; Health; Human; human MMP14 protein; improved; Incidence; Individual; Injection of therapeutic agent; Institutes; Insurance; interest; Lead; Liquid substance; Measurable; Medicare; Medicine; Methodology; Microarray Analysis; MMP2 gene; MMP9 gene; Molecular; Pain; Pathway interactions; Patient Rights; Patients; PDGFRB gene; Pharmacological Treatment; Phase; phase 1 study; Physicians; pigment epithelium-derived factor; Population; Process; Protein Microchips; Proteins; Proteome; Proteomics; PTGS2 gene; public health medicine (field); Quality of life; ranibizumab; Receptor Cell; Recruitment Activity; Research; response; Retina; Retinal Diseases; Risk; Sampling; standard of care; success; Testing; Therapeutic; Time; tool; treatment center; Treatment Cost; treatment planning; treatment response; United States; Validation; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; Vegf gene; Vision; Visual; Western Blotting; Withholding Treatment; Work