WISKOTT-ALDRICH SYNDROME: CHARACTERIZATION OF IMMUNE SYSTEM DEFECTS & GENE THERAPY PRECLINICAL STUDIES

Wiskott-Aldrich syndrome (WAS) is a severe congenital immunodeficiency for which no systematic curative treatment is available. It is caused by mutations in the gene encoding the Wiskott-Aldrich syndrome protein (WASP). In cells of the immune system, WASP regulates the actin cytoskeleton and is required for multiple functions including migration, antigen presentation and T cell effector functions. The first goal of this project is to further characterize the cellular defects in WAS and to understand how they determine the clinical manifestations of the disease including susceptibility to infection and development of autoimmunity. The second goal is to complete preclinical studies of efficacy and safety of an in vitro gene therapy approach. These studies will pave the way to the gene therapy clinical trial planned for the coming years.