Enhanced Delivery of Antibody Therapy Using Focused Ultrasound in a Mouse Model of Parkinson’s Disease
AuthorMurphy, Devin Patrick
Magnetic Resonance Imaging
AdvisorTrouard, Theodore P.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractParkinson’s Disease (PD) is the second-most prevalent neurodegenerative disorder after Alzheimer’s Disease and affects 680,000 US adults over the age of 45 as of 2010 [Marras et al. 2018]. This disease results in a loss of dopaminergic neurons, specifically in the substantia nigra. PD has also been associated with the accumulation of toxic oligomeric variants of alpha-synuclein (-syn). Although there are several medications that can help manage symptoms for PD, there is no cure. We have successfully created antibody reagents that selectively target toxic -syn variants without binding to non-oligomeric forms of normal alpha-synuclein. However, the blood-brain barrier (BBB) is a major obstacle for drug delivery and treatment of PD due to its low permeability to foreign objects. Due to the size of the monoclonal antibody, it is unable to cross the BBB without transporter proteins or temporary disruption of the BBB. This antibody therapy is delivered using novel magnetic resonance guided focused ultrasound (MRgFUS) treatment, which transiently disrupts tight junctions between epithelial cells in the BBB, resulting in gaps large enough for the antibody therapy to cross the BBB. Results indicate that the BBB was successfully opened over multiple timepoints, and the procedure does not cause extensive tissue damage. The results also show that the targeted antibody selectively binds to toxic -syn in regions of the brain where the BBB has been temporarily disrupted. Future work includes longitudinal studies to determine if this treatment combination can delay disease progression or improve quality of life in murine models of Parkinson’s Disease.
Degree ProgramGraduate College