Summary
Retinopathies constitute an extreme societal and socioeconomic burden that is expected to increase with an aging population and the increased prevalence of diabetes. These diseases, including age-related macular degeneration and proliferative diabetic retinopathy share neovascularization as a common etiology involving the pathological growth of retinal capillaries leading to blindness if left untreated. Current treatment modalities involve specialized injections into the eye that require not only outpatient visits to specialized treatment centers but are also associated with significant adverse effects. Orally bioavailable medications could revolutionize the treatment of retinopathies, by reducing adverse effects, sustaining vision, lowering the direct and indirect financial burden associated with these diseases, and increasing access to healthcare. Inspired by this idea, we have developed an approach that can be exploited to target essentially any therapeutic molecule to the eye. Our novel strategy of drug targeting will not only enrich the modified molecules in retinal tissue but will also reduce the therapeutic oral dose compared to existing anti-angiogenic therapy in cancer thereby increasing the safety of the treatment. This is achieved by absorbing a minute amount of the chemically and biologically stable molecules resulting in an extremely low plasma concentration and relying on a biological mechanism in the eye to activate the molecules to tether them to retinal target receptors and thereby extracting them from the blood. In the present application, we propose to demonstrate proof-of-concept of this strategy by modifying inhibitors of the vascular endothelial growth factor receptor (VEGFR). VEGFR is an endothelial receptor tyrosine kinase that is a key mediator of angiogenesis and an established drug target for the treatment of retinopathies. Our approach will elicit a paradigm shift in how we design future drug delivery strategies to the retina.
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| Web resources: | https://cordis.europa.eu/project/id/101047120 |
| Start date: | 01-03-2022 |
| End date: | 28-02-2026 |
| Total budget - Public funding: | 2 988 434,75 Euro - 2 988 434,00 Euro |
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Original description
Retinopathies constitute an extreme societal and socioeconomic burden that is expected to increase with an aging population and the increased prevalence of diabetes. These diseases, including age-related macular degeneration and proliferative diabetic retinopathy share neovascularization as a common etiology involving the pathological growth of retinal capillaries leading to blindness if left untreated. Current treatment modalities involve specialized injections into the eye that require not only outpatient visits to specialized treatment centers but are also associated with significant adverse effects. Orally bioavailable medications could revolutionize the treatment of retinopathies, by reducing adverse effects, sustaining vision, lowering the direct and indirect financial burden associated with these diseases, and increasing access to healthcare. Inspired by this idea, we have developed an approach that can be exploited to target essentially any therapeutic molecule to the eye. Our novel strategy of drug targeting will not only enrich the modified molecules in retinal tissue but will also reduce the therapeutic oral dose compared to existing anti-angiogenic therapy in cancer thereby increasing the safety of the treatment. This is achieved by absorbing a minute amount of the chemically and biologically stable molecules resulting in an extremely low plasma concentration and relying on a biological mechanism in the eye to activate the molecules to tether them to retinal target receptors and thereby extracting them from the blood. In the present application, we propose to demonstrate proof-of-concept of this strategy by modifying inhibitors of the vascular endothelial growth factor receptor (VEGFR). VEGFR is an endothelial receptor tyrosine kinase that is a key mediator of angiogenesis and an established drug target for the treatment of retinopathies. Our approach will elicit a paradigm shift in how we design future drug delivery strategies to the retina.Status
SIGNEDCall topic
HORIZON-EIC-2021-PATHFINDEROPEN-01-01Update Date
09-02-2023
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