Exploring RNAi technology for the treatment of Huntington's disease

Huntington’s disease (HD) is a debilitating genetic disease affecting approximately one in 10,000 individuals. HD is the most common inherited brain disease and is caused by an abnormal protein called mutant huntingtin (muHtt). Symptoms of the disease include cognitive impairment, motor dysfunction and psychiatric disturbances that usually develop around midlife. Many treatments are under investigation in mouse models of HD to potentially cure this debilitating disease. While some pharmacological agents show promise in treating HD, most act on isolated or late-onset symptoms that fail to target the disease’s greatest underlying pathological insult, the muHtt protein itself. Laura Wagner’s research is exploring RNA interference (RNAi), a natural cellular mechanism with intriguing therapeutic potential to block production of the muHtt protein in hopes of slowing or preventing HD symptoms before they start. She is using a transgenic model of HD to test RNAi constructs and their ability to prevent muHtt expression in the brain. The model will be monitored for brain changes as well as behavioural and motor function improvements as indicators of the effectiveness of RNAi treatment. In addition to testing a novel treatment for HD, this research will contribute to continued efforts in advancing medical care from a late-stage symptomatic approach to earlier, preventative therapies such as gene-targeted treatments.