Grant: Operating Grant

Fragile X syndrome (FXS), a neurodevelopmental disorder and a syndromic form of autism, is the most common inherited cause of mental retardation. In addition to varying degrees of mental retardation, persons with FXS display hyperactivity, social anxiety, autistic characteristics, and seizures (Hampson et al., 2012). Our laboratory uses an excellent animal model of this human mental disorder called the FXS knockout mouse. This mutant mouse is abnormal in that the protein product of the missing gene, called "Fragile X Mental Retardation Protein (FMRP)" is missing in these mice, as it is in humans with FXS. We hypothesize that the documented impairments in the behaviour of FXS knockout mice are caused by the lack of FMRP in certain brain regions, and that reintroduction of this missing protein into the brain of the FXS mouse using a viral vector encoding the missing gene, will restore at least some of these functions. This therapeutic strategy is termed virally-mediated gene therapy. The goal is to create an appropriate expression vector, inject it into the brain of the FXS mouse, and subsequently determine if restoration of anatomical, cellular, and behavioural impairments has occurred. The experimental strategies and methods that we will develop in this project are potentially applicable to not only persons with FXS, but also to other neurological disorders where a key brain protein is missing, reduced or abnormal. Examples include other autistic syndromes such as Rett and Angelman syndrome, lysosomal storage diseases such as adrenoleukodystrophy, and possibly some neurodegenerative diseases such as Parkinson's disease, Huntington's diseases, and amyotrophic lateral sclerosis.