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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 Statement
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: | 4 View Download Statistics |
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