Evidence map›Paper›PMID 30264465›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2018

Noninvasive delivery of an α-synuclein gene silencing vector with magnetic resonance-guided focused ultrasound.

Kristiana Xhima, Fadl Nabbouh, Kullervo Hynynen, Isabelle Aubert, Anurag Tandon

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

  1. Pooled it
  2. Focused Ultrasound for the Treatment of Circuit and Molecular Pathology in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Kristiana XhimaSunnybrook Research Institute, Toronto, Ontario, Canada.
Fadl NabbouhTanz Centre for Research in Neurodegenerative Diseases, Toronto, Ontario, Canada.
Kullervo HynynenSunnybrook Research Institute, Toronto, Ontario, Canada.
Isabelle AubertSunnybrook Research Institute, Toronto, Ontario, Canada.
Anurag TandonTanz Centre for Research in Neurodegenerative Diseases, Toronto, Ontario, Canada.
Occupational Cancer Research Centre · CAUniversity of Toronto · CASunnybrook Research Institute

Funding

Ultrasound Therapy Delivery Through Intact SkullR01EB003268 · NIBIB · SUNNYBROOK & WOMEN'S COLL HLTH SCIS CTR · PI HYNYNEN, KULLERVO · 2003 to 2020
$8.2M
fundRefName="Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST) Program">Science and TechnologyNational Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health R01 EB003268NIBIB NIH HHS R01 EB003268Weston Brain Institute and the Canadian Institutes of Health Research operating grants to A.T. FRN 119312Weston Brain Institute and the Canadian Institutes of Health Research operating grants to A.T. FRN137064Weston Brain Institute and the Canadian Institutes of Health Research operating grants to A.T. MOP130321Weston Brain Institute and the Canadian Institutes of Health Research operating grants to A.T. PJT148736
6 · The paper itself

Abstract

backgroundThe characteristic progression of Lewy pathology in Parkinson's disease likely involves intercellular exchange and the accumulation of misfolded α-synuclein amplified by a prion-like self-templating mechanism. Silencing of the α-synuclein gene could provide long-lasting disease-modifying benefits by reducing the requisite substrate for the spreading aggregation.

objectivesAs a result of the poor penetration of viral vectors across the blood-brain 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-intensity magnetic resonance-guided focused ultrasound and intravenous microbubbles that can transiently increase the access of brain impermeant therapeutic macromolecules to targeted brain regions.

methodsTransgenic mice expressing human α-synuclein were subjected to magnetic resonance-guided focused ultrasound targeted to 4 brain regions (hippocampus, substantia nigra, olfactory bulb, and dorsal motor nucleus) in tandem with intravenous microbubbles and an adeno-associated virus serotype 9 vector bearing a short hairpin RNA sequence targeting the α-synuclein gene.

resultsOne month following treatment, α-synuclein 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.

conclusionsThese results demonstrate that magnetic resonance-guided focused ultrasound can effectively, noninvasively, and simultaneously deliver viral vectors targeting α-synuclein 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. © 2018 International Parkinson and Movement Disorder Society.

Indexed as

Ultrasonographyalpha-SynucleinAnimalsApoptosisBrainCalcium-Binding ProteinsCaspase 3Cell DeathDependovirusGene Expression RegulationGene SilencingGlial Fibrillary Acidic ProteinGreen Fluorescent ProteinsHumansIn Situ Nick-End LabelingMagnetic Resonance ImagingAif1 protein, mousealpha-SynucleinCalcium-Binding ProteinsCaspase 3Glial Fibrillary Acidic ProteinGreen Fluorescent ProteinsMicrofilament ProteinsRNA, Small InterferingSynaptophysinTyrosine 3-Monooxygenaseadeno-associated virusblood-brain barriergene therapyinhibitory RNAParkinson's disease

Identifiers

PMID30264465
PMCPMC6282171
OpenAlexW2892946876

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.