PMID- 23185011
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 50
DP  - 2012 Dec 11
TI  - Wnt7a treatment ameliorates muscular dystrophy.
PG  - 20614-9
LID - 10.1073/pnas.1215765109 [doi]
AB  - Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder of 
      childhood marked by progressive debilitating muscle weakness and wasting, and 
      ultimately death in the second or third decade of life. Wnt7a signaling through 
      its receptor Fzd7 accelerates and augments regeneration by stimulating satellite 
      stem cell expansion through the planar cell polarity pathway, as well as myofiber 
      hypertrophy through the AKT/mammalian target of rapamycin (mTOR) anabolic 
      pathway. We investigated the therapeutic potential of the secreted factor Wnt7a 
      for focal treatment of dystrophic DMD muscles using the mdx mouse model, and 
      found that Wnt7a treatment efficiently induced satellite cell expansion and 
      myofiber hypertrophy in treated mucles in mdx mice. Importantly, Wnt7a treatment 
      resulted in a significant increase in muscle strength, as determined by 
      generation of specific force. Furthermore, Wnt7a reduced the level of contractile 
      damage, likely by inducing a shift in fiber type toward slow-twitch. Finally, we 
      found that Wnt7a similarly induced myotube hypertrophy and a shift in fiber type 
      toward slow-twitch in human primary myotubes. Taken together, our findings 
      suggest that Wnt7a is a promising candidate for development as an ameliorative 
      treatment for DMD.
FAU - von Maltzahn, Julia
AU  - von Maltzahn J
AD  - Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, 
      ON, Canada K1H 8L6.
FAU - Renaud, Jean-Marc
AU  - Renaud JM
FAU - Parise, Gianni
AU  - Parise G
FAU - Rudnicki, Michael A
AU  - Rudnicki MA
LA  - eng
GR  - Howard Hughes Medical Institute/United States
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121126
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (MEF2 Transcription Factors)
RN  - 0 (Mef2c protein, mouse)
RN  - 0 (Myogenic Regulatory Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt7a protein, mouse)
SB  - IM
MH  - Animals
MH  - Electrochemotherapy
MH  - Gene Knockdown Techniques
MH  - Genetic Therapy
MH  - Humans
MH  - MEF2 Transcription Factors
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred mdx
MH  - Muscle Contraction/physiology
MH  - Muscle, Skeletal/pathology/physiopathology
MH  - Muscular Dystrophy, Animal/*drug therapy/genetics/pathology/physiopathology
MH  - Myogenic Regulatory Factors/genetics/metabolism
MH  - Plasmids/administration & dosage/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - Regeneration/physiology
MH  - Signal Transduction
MH  - Wnt Proteins/genetics/physiology/*therapeutic use
PMC - PMC3528612
COIS- Conflict of interest statement: M.A.R. is a founding scientist with Fate 
      Therapeutics, who is developing Wnt7a as a therapeutic agent.
EDAT- 2012/11/28 06:00
MHDA- 2013/03/01 06:00
PMCR- 2012/11/26
CRDT- 2012/11/28 06:00
PHST- 2012/11/28 06:00 [entrez]
PHST- 2012/11/28 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
PHST- 2012/11/26 00:00 [pmc-release]
AID - 1215765109 [pii]
AID - 201215765 [pii]
AID - 10.1073/pnas.1215765109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20614-9. doi: 
      10.1073/pnas.1215765109. Epub 2012 Nov 26.