Plastin 3 promotes motor neuron axonal growth and extends survival in a mouse model of spinal muscular atrophy
journal contributionposted on 2023-05-20, 05:39 authored by Alrafiah, A, Karyka, E, Coldicott, I, Iremonger, K, Katherine LewisKatherine Lewis, Ning, K, Azzouz, M
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.
Publication titleMolecular Therapy - Methods & Clinical Development
Department/SchoolMenzies Institute for Medical Research
Place of publicationNetherlands
Rights statementCopyright 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/