Grant: Project Grant

Autism is one of the most common neurodevelopmental conditions both in Canada and worldwide. Although symptoms can vary significantly from person to person, the core symptoms affect social interactions as well as motor and sensory functions. They are present in early childhood and can cause significant challenges in daily living throughout the life of affected individuals. As autism is increasingly recognized and diagnosed, our societies are yet to provide sufficient support to individuals on the spectrum. Despite intensive research in recent years, the underlying neurobiological mechanisms of autism remain largely unclear, which hinders development of effective ways to support autistic individuals. Fragile X Syndrome (FXS) is the leading inherited cause of autism and intellectual disability. It is caused by mutations that silence the fmr1 gene located on the X chromosome and subsequent loss of the Fragile X Messenger Ribonucleoprotein (FMRP) it encodes. FMRP performs several key functions during neurodevelopment. Absence of FMRP in FXS leads to changes in intracellular signalling, notably the extracellular signal-regulated kinase (ERK) pathway, which is considered a key player in autism in general. Our team discovered that treatment with a selective inhibitor of ERK signaling improved a wide range of phenotypes in well-established mouse models of autism and FXS. Proposed experiments will further provide translatable information of targeting ERK signalling using this inhibitor, and detailed cellular and neural network mechanisms that underlie the effects of the inhibitor. This proposal will provide new knowledge and mechanistic insights of targeting ERK signalling as a potential therapeutic approach for FXS, which may ultimately help support affected individuals to improve their quality of life and achieve their full potential.