Membrane homeostasis as potential therapeutic angle in Cohen Syndrome
Awardee: Jens Luders
Institution: Institute for Research in Biomedicine, Barcelona, Spain
Grant Amount: $47,161.00
Funding Period: February 1, 2022 - January 31, 2023
Summary:
Cohen Syndrome is a rare disease caused by mutations in the VPS13B gene. Patients affected by this disease are born with several disabilities and health problems. For example, children with Cohen Syndrome may develop slowly, have a small head size, intellectual disability, and an overall weak muscle tone. They frequently suffer from a reduction in the number of certain blood cells, which increases the risk of infections, and loss of vision, which becomes worse with age and can lead to blindness. Unfortunately, there is no treatment available for these patients. Since the molecular and cellular functions of the VPS13B gene are still poorly understood, it is unclear how its mutation leads to Cohen Syndrome. This makes it impossible to develop a treatment or therapy. We have recently obtained preliminary data suggesting that Cohen Syndrome may involve defects in primary cilia, hair-like structures on the surface of cells that function as a cell's antenna. They allow cells to receive and respond to signals from their environment and are very important for various developmental processes including formation of the brain and the retina. In this project we will uncover how defects in VPS13B may affect cilium formation and function in three different model systems: cultured cells including cells obtained from Cohen Syndrome patients, retinal tissue grown in a culture dish from patient cells, and zebrafish embryos, which recapitulate many developmental processes that also occur in humans including brain and eye development. Using the same model systems, we will then test if culture supplements or pharmacological treatments may be used to repair ciliary defects. If so, these treatments may be further developed into therapies in the future.