Grant: Operating Grant

More than 500 000 Canadian children under 14 years of age suffer from intellectual disability (ID). 1.3 billion dollars is spent each year in Canada for schooling and specialized medical services for these children. An increasing number of cases of ID are now known to be caused by genetic defects. The most common cause is a defective gene called Fmr1, which causes Fragile X syndrome (FX). Children with FXS suffer from ID, and may also suffer from autism and/or epilepsy. Unfortunately, no treatment option is available for FX. Thus, it would be useful to have an animal model system for experiments to learn how a defect in the Fmr1 gene leads to ID and the other problems associated with FX. FX is a complex disease, but mice and fruit flies (Drosophila) with defective Fmr1 genes have learning problems like those observed in human FX patients. Fruit flies have been used for decades to study the genetic mechanisms of memory. I have found that FXS flies have a profound memory defect. When normal flies are subjected to two odors, with one odor accompanied by a mild electrical shock, the flies quickly learn to avoid the odor with the shock. However, FX flies do not. I observed high levels of protein expression in the brains of FX flies, and, most interestingly, memory was improved by feeding the flies drugs that block protein production. Protein excess is also observed in FX patients and in those with other ID syndromes. I propose to use the FX flies and our memory assay to uncover the specific reasons why too much protein is being produced in the FX brain and then reverse the excessive protein synthesis using genetics and medication. Our findings have the potential to help treat children with FX, as well as those with other ID syndromes, epilepsy and autism.