PMID- 24115583
OWN - NLM
STAT- MEDLINE
DCOM- 20140529
LR  - 20211021
IS  - 1757-4684 (Electronic)
IS  - 1757-4676 (Print)
IS  - 1757-4676 (Linking)
VI  - 5
IP  - 11
DP  - 2013 Nov
TI  - Rescue of amyotrophic lateral sclerosis phenotype in a mouse model by intravenous 
      AAV9-ADAR2 delivery to motor neurons.
PG  - 1710-9
LID - 10.1002/emmm.201302935 [doi]
AB  - Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron 
      disease, and the lack of effective therapy results in inevitable death within a 
      few years of onset. Failure of GluA2 RNA editing resulting from downregulation of 
      the RNA-editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) occurs in the 
      majority of ALS cases and causes the death of motor neurons via a Ca(2+) 
      -permeable AMPA receptor-mediated mechanism. Here, we explored the possibility of 
      gene therapy for ALS by upregulating ADAR2 in mouse motor neurons using an 
      adeno-associated virus serotype 9 (AAV9) vector that provides gene delivery to a 
      wide array of central neurons after peripheral administration. A single 
      intravenous injection of AAV9-ADAR2 in conditional ADAR2 knockout mice (AR2), 
      which comprise a mechanistic mouse model of sporadic ALS, caused expression of 
      exogenous ADAR2 in the central neurons and effectively prevented progressive 
      motor dysfunction. Notably, AAV9-ADAR2 rescued the motor neurons of AR2 mice from 
      death by normalizing TDP-43 expression. This AAV9-mediated ADAR2 gene delivery 
      may therefore enable the development of a gene therapy for ALS.
CI  - (c) 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.
FAU - Yamashita, Takenari
AU  - Yamashita T
AD  - CREST, Japan Science and Technology Agency, Graduate School of Medicine, 
      University of Tokyo, Bunkyo-Ku, Tokyo, Japan; Department of Neurology, Graduate 
      School of Medicine, University of Tokyo, Bunkyo-Ku, Tokyo, Japan; Center for 
      Disease Biology and Integrative Medicine, Graduate School of Medicine, The 
      University of Tokyo, Bunkyo-Ku, Tokyo, Japan.
FAU - Chai, Hui Lin
AU  - Chai HL
FAU - Teramoto, Sayaka
AU  - Teramoto S
FAU - Tsuji, Shoji
AU  - Tsuji S
FAU - Shimazaki, Kuniko
AU  - Shimazaki K
FAU - Muramatsu, Shin-ichi
AU  - Muramatsu S
FAU - Kwak, Shin
AU  - Kwak S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130924
PL  - England
TA  - EMBO Mol Med
JT  - EMBO molecular medicine
JID - 101487380
RN  - 0 (RNA-Binding Proteins)
RN  - EC 3.5.4.4 (ADARB1 protein, human)
RN  - EC 3.5.4.4 (Adenosine Deaminase)
SB  - IM
MH  - Adenosine Deaminase/*genetics/metabolism
MH  - Amyotrophic Lateral Sclerosis/*enzymology/genetics/therapy
MH  - Animals
MH  - Brain/cytology/enzymology/virology
MH  - Dependovirus/genetics/physiology
MH  - Disease Models, Animal
MH  - *Genetic Therapy
MH  - Genetic Vectors/genetics/physiology
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Motor Neurons/*enzymology
MH  - RNA-Binding Proteins/*genetics/metabolism
PMC - PMC3840487
OTO - NOTNLM
OT  - AMPA receptor
OT  - adeno-associated virus (AAV) 9
OT  - adenosine deaminase acting on RNA 2 (ADAR2)
OT  - amyotrophic lateral sclerosis (ALS)
OT  - gene therapy
EDAT- 2013/10/12 06:00
MHDA- 2014/05/30 06:00
PMCR- 2013/11/01
CRDT- 2013/10/12 06:00
PHST- 2013/04/22 00:00 [received]
PHST- 2013/08/23 00:00 [revised]
PHST- 2013/08/23 00:00 [accepted]
PHST- 2013/10/12 06:00 [entrez]
PHST- 2013/10/12 06:00 [pubmed]
PHST- 2014/05/30 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - 10.1002/emmm.201302935 [doi]
PST - ppublish
SO  - EMBO Mol Med. 2013 Nov;5(11):1710-9. doi: 10.1002/emmm.201302935. Epub 2013 Sep 
      24.