Evidence map›Paper›PMID 31501034›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology.

María Izco, Javier Blesa, Martin Schleef, Marco Schmeer, Riccardo Porcari, Raya Al-Shawi, Stephan Ellmerich, María de Toro, Chris Gardiner, Yiqi Seow and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

116 citing papers in PubMed, 1 synthesis or guideline pooled it.

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56 more citing papers are in PubMed but not listed here.

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

16 authors.

María IzcoLaboratory of Molecular Neurobiology, Center for Biomedical Research of La Rioja (CIBIR), Logroño 26006, La Rioja, Spain.
Javier BlesaHM CINAC, Hospital Universitario HM Puerta del Sur, Mostoles 28938, Madrid, Spain.
Martin SchleefPlasmidFactory GmbH & Co. KG, Bielefeld 33607, Germany.
Marco SchmeerPlasmidFactory GmbH & Co. KG, Bielefeld 33607, Germany.
Riccardo PorcariWolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London NW3 2PF, UK.
Raya Al-ShawiWolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London NW3 2PF, UK; Centre for Biomedical Science, Division of Medicine, University College London, London NW3 2PF, UK.
Stephan EllmerichWolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London NW3 2PF, UK.
María de ToroGenomics and Bioinformatics Core Facility, Center for Biomedical Research of La Rioja (CIBIR), Logroño 26006, La Rioja, Spain.
Chris GardinerDepartment of Haematology, University College London, London NW3 2PF, UK.
Yiqi SeowMolecular Engineering Laboratory, Biomedical Sciences Institutes, A*STAR, Singapore 138668, Singapore.
Alejandro Reinares-SebastianHM CINAC, Hospital Universitario HM Puerta del Sur, Mostoles 28938, Madrid, Spain.
Raquel ForcenLaboratory of Molecular Neurobiology, Center for Biomedical Research of La Rioja (CIBIR), Logroño 26006, La Rioja, Spain.
J Paul SimonsWolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London NW3 2PF, UK; Centre for Biomedical Science, Division of Medicine, University College London, London NW3 2PF, UK.
Vittorio BellottiWolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London NW3 2PF, UK.
J Mark CooperDepartment of Clinical Neuroscience, Institute of Neurology, University College London, London NW3 2PF, UK.
Lydia Alvarez-ErvitiLaboratory of Molecular Neurobiology, Center for Biomedical Research of La Rioja (CIBIR), Logroño 26006, La Rioja, Spain; Department of Clinical Neuroscience, Institute of Neurology, University College London, London NW3 2PF, UK. Electronic address: laerviti@riojasalud.es.

Funding

Medical Research Council MR/K000187/1Parkinson's UK F-1101
6 · The paper itself

Abstract

The development of new therapies to slow down or halt the progression of Parkinson's disease is a health care priority. A key pathological feature is the presence of alpha-synuclein aggregates, and there is increasing evidence that alpha-synuclein propagation plays a central role in disease progression. Consequently, the downregulation of alpha-synuclein is a potential therapeutic target. As a chronic disease, the ideal treatment will be minimally invasive and effective in the long-term. Knockdown of gene expression has clear potential, and siRNAs specific to alpha-synuclein have been designed; however, the efficacy of siRNA treatment is limited by its short-term efficacy. To combat this, we designed shRNA minicircles (shRNA-MCs), with the potential for prolonged effectiveness, and used RVG-exosomes as the vehicle for specific delivery into the brain. We optimized this system using transgenic mice expressing GFP and demonstrated its ability to downregulate GFP protein expression in the brain for up to 6 weeks. RVG-exosomes were used to deliver anti-alpha-synuclein shRNA-MC therapy to the alpha-synuclein preformed-fibril-induced model of parkinsonism. This therapy decreased alpha-synuclein aggregation, reduced the loss of dopaminergic neurons, and improved the clinical symptoms. Our results confirm the therapeutic potential of shRNA-MCs delivered by RVG-exosomes for long-term treatment of neurodegenerative diseases.

Indexed as

Disease Models, AnimalDrug Delivery Systemsalpha-SynucleinAnimalsBrainExosomesGene Expression RegulationGenetic TherapyHumansMaleMiceMice, Inbred C3HMice, Inbred C57BLMice, TransgenicParkinson DiseaseRNA, Small Interferingalpha-SynucleinRNA, Small Interferingalpha-synucleinexosomesgene therapyParkinson’s diseaseshRNA minicircle

Identifiers

PMID31501034
PMCPMC6904801

What OpenQuestion holds

Textmetadata
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.