Fragile X syndrome (FXS) is the most common inherited cause of cognitive impairment and autism. In addition to varying degrees of cognitive impairment, 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 line is abnormal in that the protein product of the missing gene, a protein called "Fragile X Mental Retardation Protein (FMRP)" is missing in these mice, as in humans with FXS. We hypothesize that the documented impairments in the behaviour of FXS knockout mice are caused primarily 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. The goal is to create an appropriate expression vector, inject it into the brain or circulatory system of the FXS mouse, and subsequently determine if restoration of anatomical, cellular, and behavioural impairments has occurred. We also plan to apply this general therapeutic strategy to another disorder effecting children, Dravet Syndrome, where severe seizures and autistic behaviours are manifest. Importantly, the first virally-mediated gene therapeutic drug (a biological-based therapeutic) was approved for use in humans was approved in Europe in 2013, and currently there are more than 10 ongoing clinical trials. Our research will seek to lay the ground work for transferring this technology for the treatment of autism and neurodevelopment disorders.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
