PMID- 28480302
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240216
IS  - 2329-0501 (Print)
IS  - 2329-0501 (Electronic)
IS  - 2329-0501 (Linking)
VI  - 5
DP  - 2017 Jun 16
TI  - Efficacy of Gene Therapy Is Dependent on Disease Progression in Dystrophic Mice 
      with Mutations in the FKRP Gene.
PG  - 31-42
LID - 10.1016/j.omtm.2017.02.002 [doi]
AB  - Loss-of-function mutations in the Fukutin-related protein (FKRP) gene cause 
      limb-girdle muscular dystrophy type 2I (LGMD2I) and other forms of congenital 
      muscular dystrophy-dystroglycanopathy that are associated with glycosylation 
      defects in the alpha-dystroglycan (alpha-DG) protein. Systemic administration of a single 
      dose of recombinant adeno-associated virus serotype 9 (AAV9) vector expressing 
      human FKRP to a mouse model of LGMD2I at various stages of disease progression 
      was evaluated. The results demonstrate rescue of functional glycosylation of alpha-DG 
      and muscle function, along with improvements in muscle structure at all disease 
      stages versus age-matched untreated cohorts. Nevertheless, mice treated in the 
      latter stages of disease progression revealed a decrease in beneficial effects of 
      the treatment. The results provide a proof of concept for future clinical trials 
      in patients with FKRP-related muscular dystrophy and demonstrate that 
      AAV-mediated gene therapy can potentially benefit patients at all stages of 
      disease progression, but earlier intervention would be highly preferred.
FAU - Vannoy, Charles Harvey
AU  - Vannoy CH
AD  - McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research 
      Center, Carolinas Medical Center, Carolinas Healthcare System, Charlotte, NC 
      28203, USA.
FAU - Xiao, Will
AU  - Xiao W
AD  - McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research 
      Center, Carolinas Medical Center, Carolinas Healthcare System, Charlotte, NC 
      28203, USA.
FAU - Lu, Peijuan
AU  - Lu P
AD  - McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research 
      Center, Carolinas Medical Center, Carolinas Healthcare System, Charlotte, NC 
      28203, USA.
FAU - Xiao, Xiao
AU  - Xiao X
AD  - Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of 
      North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
FAU - Lu, Qi Long
AU  - Lu QL
AD  - McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research 
      Center, Carolinas Medical Center, Carolinas Healthcare System, Charlotte, NC 
      28203, USA.
LA  - eng
GR  - R01 NS082536/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20170308
PL  - United States
TA  - Mol Ther Methods Clin Dev
JT  - Molecular therapy. Methods & clinical development
JID - 101624857
PMC - PMC5415313
OTO - NOTNLM
OT  - adeno-associated virus
OT  - dystroglycanopathy
OT  - fukutin-related protein
OT  - gene therapy
OT  - muscular dystrophy
EDAT- 2017/05/10 06:00
MHDA- 2017/05/10 06:01
PMCR- 2017/03/08
CRDT- 2017/05/09 06:00
PHST- 2016/12/30 00:00 [received]
PHST- 2017/02/20 00:00 [accepted]
PHST- 2017/05/09 06:00 [entrez]
PHST- 2017/05/10 06:00 [pubmed]
PHST- 2017/05/10 06:01 [medline]
PHST- 2017/03/08 00:00 [pmc-release]
AID - S2329-0501(17)30042-6 [pii]
AID - 10.1016/j.omtm.2017.02.002 [doi]
PST - epublish
SO  - Mol Ther Methods Clin Dev. 2017 Mar 8;5:31-42. doi: 10.1016/j.omtm.2017.02.002. 
      eCollection 2017 Jun 16.