A non-invasive strategy for targeted in vivo gene therapy and immunization in Parkinson’s disease

2012  -  Toronto, ON, CA


University of Toronto, Tanz Centre for Research in Neurodegenerative Diseases, Sunnybrook Health Sciences Centre

Project Description

Safe, effective, and non-invasive drug delivery into the brain remains a major challenge for the treatment of neurodegenerative disorders. Our project will evaluate a novel non-invasive approach that relies on the use of focused ultrasound to increase the permeability of the blood-brain barrier temporarily and allow drug entry into specific brain regions. In Parkinson’s disease (PD), it is clear that too much expression of a neuronal protein, known as alpha-synuclein, can cause neurodegeneration. Hence, there is an urgent need to identify safe and effective methods to reduce the brain levels of this protein. We will use different types of treatments to reduce alpha-synuclein levels in localized regions of mouse brains that correspond to affected areas in humans with PD. Because focused ultrasound is currently being assessed in human clinical trials, if we are successful in this study, our approach can quickly be adapted to test whether the suppression of alpha-synuclein expression can be safely achieved in patients with PD.

Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging

Poor penetration of drugs into the brain is a major limitation to treating neurological disorders and a critical impediment to new drug discovery. This study will evaluate whether drugs can be delivered safely and effectively using focused ultrasound to enable precise targeting and dispersion of large molecules into specific brain regions across the blood-brain barrier. Focused ultrasound is a technique that will avoid unwanted side effects that accompany surgical intervention such as unintended neural lesions, or severe hemorrhages.

Anticipated Outcome

Validation of our approach to combine gene therapy and focused ultrasound could fulfill a long sought-after goal of a therapy for neurodegeneration: delivering drugs and genes into diseased brain areas in a non-invasive manner, and resulting in long-lasting beneficial effects. Our research is expected to have therapeutic impacts for future treatments of PD and other neurological disorders.