KUS121, an ATP regulator, mitigates chorioretinal pathologies in animal models of age-related macular degeneration

Abstract Age-related macular degeneration(AMD) is a leading cause of blindness among elderly people. The appearance of drusenis a clinical manifestation and a harbinger of both exudativeand atrophic AMD. Recently, antibody-based medicines have been used to treat the exudativetype. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs) that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptortype 2-deficient mice, a mouse model of AMD. Systemic administrationof KUS121 prevented or reduced drusen-like lesions and endoplasmic reticulum stress, and then substantially mitigated chorioretinalpathologies with significant preservation of visual function. Additionally, we confirmed that long-term oral administration of KUS121 caused no systemic complications in drusen-affected monkeys. ATP regulation by KUSs may represent a novel strategy in the treatment of drusenand prevention of disease progression in AMD.