Wet age-related macular degeneration (AMD) is the most prevalent cause of severe vision loss and blindness in patients over the age of 60 in the US. Subretinal neovascularization is responsible for most severe loss of vision. A newly discovered peptide, SP6001, is promising for treating wet AMD as it works through multiple antiangiogenic mechanisms. Small peptides possess many advantageous characteristics as therapeutic agents, such as high specificity and low toxicity, but their main disadvantage is their short half-life. To counter this possible limitation, a novel retroinverted version of the peptide ill be constructed and it will be protected from degradation by being encapsulated within a polymeric particle system. The particle delivery systems will ensure safe and effective delivery of the novel antiangiogenic peptide along with its controlled release within the eye. New biomaterials and particle formulations will be synthesized and then particle properties, peptide release, and biological activity in vitro evaluated. Following experiments on human retinal endothelial cells, the particle/peptide systems will be tested in vivo in mouse models for wet AMD. Retroinverted peptide will be compared to standard and scrambled peptide and efficacy of particle formulations will be evaluated for 4 months. In vitro assays will also be performed to identify the receptors that the peptide acts on and the distribution of these receptors in the eye under normal conditions and under AMD conditions. A new validated treatment modality that can inhibit both VEGF-mediated and non-VEGF- mediated angiogenic pathways and that can reduce the frequency of necessary intravitreal injections would significantly improve the currently used treatments for AMD.
This research proposal is for the creation of a controlled release peptide delivery system to treat wet age-related macular degeneration (AMD) and its evaluation in vitro and in vivo. Following a single intravitreal injection, novel polymeric particls will release a newly discovered antiangiogenic peptide that may treat AMD for at least 4 months.
|Shmueli, Ron B; Ohnaka, Masayuki; Miki, Akiko et al. (2013) Long-term suppression of ocular neovascularization by intraocular injection of biodegradable polymeric particles containing a serpin-derived peptide. Biomaterials 34:7544-51|