Waters, S. B., Zhou, C., Nguyen, T., Zelkha, R., Lee, H., Kazlauskas, A., Rosenblatt, M. I., Malik, A. B., and Yamada, K. H., (2021), VEGFR2 Trafficking by KIF13B Is a Novel Therapeutic Target for Wet Age-Related Macular Degeneration., Investigative Ophthalmology & Visual Science doi: 10.1167/iovs.62.2.5.PMID: 33533881
Wet age-related macular degeneration (AMD) is a leading cause of vision loss for older patients. Current therapies are targeting VEGF by intravitreal injection of anti-VEGF drugs. The current therapies are effective, however, monthly injection is a big burden for old patients. Moreover, there are non-responders for anti-VEGF drugs. Even if the patients respond to anti-VEGF drugs well at the beginning, some patients become resistant to the repeated therapy. Switching the drugs with other drugs is used to overcome the resistance, thus developing novel therapy with different strategies is beneficial for the patients.
Based on the discovery that the trafficking of the receptor for VEGF is important to regulate pathological angiogenesis (1), we developed a novel strategy to inhibit VEGFR2 trafficking. Our strategy uses a small peptide disrupting the interaction between VEGFR2 and its transporter KIF13B (2). We showed the efficacy of the peptide KAI to inhibit tumor angiogenesis and tumor growth in mouse models (2). An anti-VEGF drug Avastin was also originally developed in cancer therapy and its derivative Lucentis was applied for wet AMD therapy. Both Avastin and Lucentis are effective current therapies for wet AMD. Thus, we also applied our strategy to wet AMD therapy, and it worked (3). As our peptide is a small cell-permeable peptide, topically applied peptide as eyedrop could reach the back of the eyes where the disease occurs. Using the laser-induced choroidal neovascularization (CNV) model, which is a widely accepted animal model of wet AMD, we showed the efficacy of the peptide KAI to inhibit angiogenesis in set AMD (3). Further investigation will be beneficial to develop this strategy for the therapy for wet AMD.