Developing a novel disease-targeted anti-angiogenic therapy for CNV
Ended Project Grant Awarded Last action
- Award ID
- R21EY035421
- Recipient
-
Baylor College Of Medicine UEI FXKMA43NTV21
- Awarding agency
-
National Eye Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $440,000
Award facts
- Assistance listing
- 93.867 Vision Research
- Completion date
- Originally
- Place of performance
- Texas, USA
Award details come from USAspending.gov.
Description
- Abstract
- Wet age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly in developed countries, characterized by choroidal neovascularization (CNV). The disease is currently treated by anti-vascular endothelial growth factor (vegf) drugs, such as aflibercept, but with limited efficacy and potential side effects. An unmet clinical need for wet AMD therapy is to identify disease-restricted angiogenic factors and develop novel vegf-independent disease-targeted anti-angiogenic therapies with optimal safety for alternative or combination treatment to improve the efficacy for anti-vegf-resistant patients. We applied our innovative technology of comparative ligandomics to CNV and healthy mice and discovered a novel CNV-selective angiogenic factor that selectively binds to CNV but not healthy choroidal vessels. In contrast, vegf indiscriminately drives angiogenesis. Preliminary data showed that polyclonal antibodies (pabs) against the CNV-selective angiogenic factor alleviate CNV in mice with comparable efficacy to aflibercept. However, lack of a neutralizing monoclonal antibody (MAB) against this novel target is a major obstacle to develop disease-targeted anti-angiogenic therapy for clinical translation and assess the efficacy and safety. The objective of this exploratory project is to generate and characterize neutralizing mabs against the new target. Our central hypothesis is that the neutralizing mabs against the angiogenic factor efficiently alleviate CNV with high efficacy but minimal adverse side effects to healthy retinal vessels and neurons. In aim 1, we will generate mabs against the angiogenic factor and characterize their neutralizing activity. In aim 2, we will characterize the therapeutic efficacy and safety of the neutralizing mabs. To our knowledge, all anti-angiogenic drugs, approved or in the pipeline, target conventional angiogenic factors that indiscriminately regulate both diseased and healthy vasculatures. This project has the potential to develop a novel disease-targeted vegf-independent anti-angiogenic therapy for wet AMD with minimal side effects on healthy retinal vessels and neurons. Successful development of this novel therapy will also support the innovative ligandomics technology that is broadly applicable to vascular and non-vascular diseases for pathological mechanism research and drug target discovery.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $440,000 |
Quick answers
Who received award R21EY035421?
R21EY035421 was awarded to Baylor College Of Medicine by National Eye Institute (National Institutes of Health) on September 30, 2023.
How much is award R21EY035421 worth?
$440,000 has been obligated on R21EY035421.
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