Noninvasive delivery of an α‐synuclein gene silencing vector with magnetic resonance–guided focused ultrasound

• DOI: 10.1002/mds.101
• Publication Date: 2018-09-28T09:35:01Z
• Authors: Kristiana Xhima; Fadl Nabbouh; Kullervo Hynynen; Isabelle Aubert; Anurag Tandon
• Keywords: Synaptophysin

ABSTRACT Background: The characteristic progression of Lewy pathology in Parkinson's disease likely involves intercellular exchange and the accumulation misfolded α‐synuclein amplified by a prion‐like self‐templating mechanism. Silencing gene could provide long‐lasting disease‐modifying benefits reducing requisite substrate for spreading aggregation. Objectives: As result poor penetration viral vectors across blood–brain barrier, therapy central nervous system disorders requires direct injections into affected brain regions, invasiveness is further increased need bilateral delivery to multiple regions. Here we test noninvasive approach combining low‐intensity magnetic resonance–guided focused ultrasound intravenous microbubbles that can transiently increase access impermeant therapeutic macromolecules targeted Methods: Transgenic mice expressing human were subjected 4 regions (hippocampus, substantia nigra, olfactory bulb, dorsal motor nucleus) tandem with an adeno‐associated virus serotype 9 vector bearing short hairpin RNA sequence targeting gene. Results: One month following treatment, immunoreactivity was decreased whereas other neuronal markers such as synaptophysin or tyrosine hydroxylase unchanged, cell death glial activation remained at basal levels. Conclusions: These results demonstrate effectively, noninvasively, simultaneously deliver areas. Importantly, this may be useful alter along selected pathways, particularly prodromal PD improve early diagnoses. © 2018 International Parkinson Movement Disorder Society