PMID- 29552580
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220129
IS  - 2329-0501 (Print)
IS  - 2329-0501 (Electronic)
IS  - 2329-0501 (Linking)
VI  - 9
DP  - 2018 Jun 15
TI  - Plastin 3 Promotes Motor Neuron Axonal Growth and Extends Survival in a Mouse 
      Model of Spinal Muscular Atrophy.
PG  - 81-89
LID - 10.1016/j.omtm.2018.01.007 [doi]
AB  - 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.
FAU - Alrafiah, Aziza
AU  - Alrafiah A
AD  - Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a 
      Glossop Road, S10 2HQ Sheffield, UK.
AD  - Faculty of Applied Medical Sciences, King Abdulaziz University, P.O Box 80200, 
      Jeddah 21589, Saudi Arabia.
FAU - Karyka, Evangelia
AU  - Karyka E
AD  - Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a 
      Glossop Road, S10 2HQ Sheffield, UK.
FAU - Coldicott, Ian
AU  - Coldicott I
AD  - Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a 
      Glossop Road, S10 2HQ Sheffield, UK.
FAU - Iremonger, Kayleigh
AU  - Iremonger K
AD  - Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a 
      Glossop Road, S10 2HQ Sheffield, UK.
FAU - Lewis, Katherin E
AU  - Lewis KE
AD  - Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a 
      Glossop Road, S10 2HQ Sheffield, UK.
FAU - Ning, Ke
AU  - Ning K
AD  - Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a 
      Glossop Road, S10 2HQ Sheffield, UK.
FAU - Azzouz, Mimoun
AU  - Azzouz M
AD  - Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a 
      Glossop Road, S10 2HQ Sheffield, UK.
LA  - eng
GR  - 294745/ERC_/European Research Council/International
GR  - G1001492/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20180131
PL  - United States
TA  - Mol Ther Methods Clin Dev
JT  - Molecular therapy. Methods & clinical development
JID - 101624857
PMC - PMC5852384
OTO - NOTNLM
OT  - SMA
OT  - gene therapy
OT  - plastin 3
EDAT- 2018/03/20 06:00
MHDA- 2018/03/20 06:01
PMCR- 2018/01/31
CRDT- 2018/03/20 06:00
PHST- 2017/10/31 00:00 [received]
PHST- 2018/01/15 00:00 [accepted]
PHST- 2018/03/20 06:00 [entrez]
PHST- 2018/03/20 06:00 [pubmed]
PHST- 2018/03/20 06:01 [medline]
PHST- 2018/01/31 00:00 [pmc-release]
AID - S2329-0501(18)30008-1 [pii]
AID - 10.1016/j.omtm.2018.01.007 [doi]
PST - epublish
SO  - Mol Ther Methods Clin Dev. 2018 Jan 31;9:81-89. doi: 10.1016/j.omtm.2018.01.007. 
      eCollection 2018 Jun 15.