Grant: Project Grant

Alpha-Synuclein (a-syn) is a key factor in Parkinson's disease (PD) and other neurodegenerative disorders known collectively as synucleinopathies. The main pathology common to these brain disorders is a progressive and selective accumulation of sticky deposits of a-syn within dying neurons in the brains of affected individuals. Recent studies suggest that these sticky accumulations of a-syn can be passed from sick neurons to healthy ones, and thereby causing the spread and progression of the disease. Therefore, it is believed that therapies designed to reduce a-syn expression hold significant promise to alleviate PD symptoms. Here we will use gene therapy to inhibit expression of brain a-syn. However, because the brain is generally quite impenetrable to drugs given by the usual means, ie injection or oral, we will circumvent this resistance by using a novel technique, called focused ultrasound, to enable the entry of gene vectors into the brain. Our goal is to inject gene vectors intravenously into synucleinopathy-affected mice. To target these vectors into the brain, we will use focused ultrasound in order to make affected brain areas more permeable to the gene vectors.. Following the treatment, we will assess the extent of behavioural and pathological improvements. Our optimal expectation is that there will be a reduction in the movement impairments and the less a-syn accumulation in animals that received both the ultrasound and gene therapy.