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Plastin 3 promotes motor neuron axonal growth and extends survival in a mouse model of spinal muscular atrophy

Citation

Alrafiah, A and Karyka, E and Coldicott, I and Iremonger, K and Lewis, KE and Ning, K and Azzouz, M, Plastin 3 promotes motor neuron axonal growth and extends survival in a mouse model of spinal muscular atrophy, Molecular Therapy - Methods & Clinical Development, 9 pp. 81-89. ISSN 2329-0501 (2018) [Refereed Article]


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Copyright 2018 The Author(s). Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) http://creativecommons.org/licenses/by-nc-nd/4.0/

DOI: doi:10.1016/j.omtm.2018.01.007

Abstract

Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease. SMA is caused by mutations in the survival motor neuron gene (SMN1), leading to reduced levels of SMN protein in the CNS. The actin-binding protein plastin 3 (PLS3) has been reported as a modifier for SMA, making it a potential therapeutic target. Here, we show reduced levels of PLS3 protein in the brain and spinal cord of a mouse model of SMA. Our study also revealed that lentiviral-mediated PLS3 expression restored axonal length in cultured Smn-deficient motor neurons. Delivery of adeno-associated virus serotype 9 (AAV9) harboring Pls3 cDNA via cisterna magna in SMNΔ7 mice, a widely used animal model of SMA, led to high neuronal transduction efficiency. PLS3 treatment allowed a small but significant increase of lifespan by 42%. Although there was no improvement of phenotype, this study has demonstrated the potential use of Pls3 as a target for gene therapy, possibly in combination with other disease modifiers.

Item Details

Item Type:Refereed Article
Keywords:spinal muscular atrophy, plastin 3, gene therapy
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
UTAS Author:Lewis, KE (Dr Katherine Lewis)
ID Code:133953
Year Published:2018
Web of Science® Times Cited:5
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-07-17
Last Modified:2019-08-08
Downloads:1 View Download Statistics

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