| First Author | Alrafiah A | Year | 2018 |
| Journal | Mol Ther Methods Clin Dev | Volume | 9 |
| Pages | 81-89 | PubMed ID | 29552580 |
| Mgi Jnum | J:281772 | Mgi Id | MGI:6381121 |
| Doi | 10.1016/j.omtm.2018.01.007 | Citation | Alrafiah A, et al. (2018) Plastin 3 Promotes Motor Neuron Axonal Growth and Extends Survival in a Mouse Model of Spinal Muscular Atrophy. Mol Ther Methods Clin Dev 9:81-89 |
| abstractText | 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 SMNDelta7 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. |
