Grant: CIHR Fellowship

Huntington disease (HD) is an inherited neurodegenerative disease that affects 1 in every 7000 individuals worldwide. HD manifests as a spectrum of movement, cognitive and psychiatric symptoms that typically first appear in adulthood and progressively worsen until death. Currently, there are no effective treatments to prevent or even slow progression of HD. Unaffected individuals have two normal copies of the HTT gene, but inheriting a single mutated copy of HTT from either parent is sufficient to cause HD. The mutated HTT gene codes for production of the toxic, mutant huntingtin protein that is responsible for killing brain cells in HD. Notably, the other, non-mutated (or normal) copy of the huntingtin protein is critical for the health of brain cells. Therefore, a drug that targets the cause of the disease by preventing production of the toxic mutant protein, without affecting levels of the beneficial normal protein, would represent the most promising strategy for treating HD. Our group has developed specialized molecules that bind to target sequences found in the mutant HTT gene and prevent production of the toxic mutant protein. However, due to HTT gene sequence differences between individuals with HD, targeting a single sequence variation in the mutant message would only provide a treatment option for a portion of the HD population. Therefore, I propose to develop a treatment strategy using multiple specialized molecules targeting the most common sequence variations found in the HD population to provide a personalized therapeutic option for every HD patient in the world.