Development of a non-invasive oral prodrug targeting β-galactosidase in senescent cells for the treatment of age-related macular degeneration

Abstract

A common treatment for age-related macular degeneration is to inject it into the eye finer than the hair. This treatment method causes fear in the patient because the needle is visible, so we try to develop an oral prodrug to reduce the patient's fear. Oral drug delivery has many advantages, including high patient compliance, low cost, and ease of use. Based on these advantages, we are trying to develop a new oral prodrug for the treatment of age-related macular degeneration (AMD). To develop new oral drugs that can maintain toxicity while linking specific linkers to existing drugs that are too toxic to senescent cells to increase selectivity. In retinal pigment epithelial cells within AMD, the prodrug can function as a drug that can be specifically cleaved and used by enzymes overexpressed in aging cells. The β-galactosidase protein overexpressed in AMD is a hydrolase that can be used as a biomarker for aging and catalyzes hydrolysis only in aged cells. Therefore, we are trying to develop a new oral prodrug N201-gal that can be cleaved by β-galactosidase proteins that target aging retinal pigment epithelial cells. N201-gal travels through the mouth, stomach, and internal organs to blood vessels and reaches the eyes. Finally, in the senescent retinal pigment epithelial cells of the eye, N201-gal can kill aging cell lines as a highly toxic drug when converted to N201. As a result, new oral prodrug N201-gal, that can deliver an N201 drug cleaved by the β-galactosidase protein from macular degenerated cells to kill aging cells.