Development of in vivo therapeutic strategies for pain and pruritus in Olmsted syndrome

Olmsted syndrome (OS) is a disabling skin genetic disease that causes painful thickening of the skin on palms and soles and around the mouth, ears, nose. The symptoms are so severe that spontaneous amputation of digits may occur. OS patients find it difficult to walk, grasp objects, and write. OS not only is a disease of keratinocytes, the cells that compose the skin layers, but it also affects skin sensory nerves and OS patients suffer from debilitating chronic pain and itch. Currently, no effective treatments are available to effectively manage OS symptoms. The aim of this project is to investigate the molecular mechanisms underlying OS. The first step to achieve this result is to understand whether available mouse lines can be used to model human OS, and to generate genetically modified mice that will help us visualize the skin defects in great details at a microscopic level. We will monitor scratching and pain behaviors in mice, and correlate them with microscopic skin morphology. Establishing an OS mouse models will allow us and other scientists in the future to tease apart the different pathological components of OS deriving from keratinocytes or skin sensory nerves malfunctions. Importantly, our mouse models will help us to design mechanism based therapeutic options to treat OS symptoms by locally targeting sensitized pain and itch neurons