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Silencing of the \u03b1\u2010synuclein gene could provide long\u2010lasting disease\u2010modifying benefits by reducing the requisite substrate for the spreading aggregation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objectives:<\/jats:bold>\n                    As a result of the poor penetration of viral vectors across the blood\u2013brain barrier, gene therapy for central nervous system disorders requires direct injections into the affected brain regions, and invasiveness is further increased by the need for bilateral delivery to multiple brain regions. Here we test a noninvasive approach by combining low\u2010intensity magnetic resonance\u2013guided focused ultrasound and intravenous microbubbles that can transiently increase the access of brain impermeant therapeutic macromolecules to targeted brain regions.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Transgenic mice expressing human \u03b1\u2010synuclein were subjected to magnetic resonance\u2013guided focused ultrasound targeted to 4 brain regions (hippocampus, substantia nigra, olfactory bulb, and dorsal motor nucleus) in tandem with intravenous microbubbles and an adeno\u2010associated virus serotype 9 vector bearing a short hairpin RNA sequence targeting the \u03b1\u2010synuclein gene.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    One month following treatment, \u03b1\u2010synuclein immunoreactivity was decreased in targeted brain regions, whereas other neuronal markers such as synaptophysin or tyrosine hydroxylase were unchanged, and cell death and glial activation remained at basal levels.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    These results demonstrate that magnetic resonance\u2013guided focused ultrasound can effectively, noninvasively, and simultaneously deliver viral vectors targeting \u03b1\u2010synuclein to multiple brain areas. Importantly, this approach may be useful to alter the progression of Lewy pathology along selected neuronal pathways, particularly as prodromal PD markers improve early diagnoses. \u00a9 2018 International Parkinson and Movement Disorder Society\n                  <\/jats:p>","DOI":"10.1002\/mds.101","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T05:35:01Z","timestamp":1538112901000},"page":"1567-1579","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Noninvasive delivery of an \u03b1\u2010synuclein gene silencing vector with magnetic resonance\u2013guided focused ultrasound"],"prefix":"10.1002","volume":"33","author":[{"given":"Kristiana","family":"Xhima","sequence":"first","affiliation":[{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"},{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario 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