PMID- 17426713
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20220309
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 15
IP  - 6
DP  - 2007 Jun
TI  - Sustained AAV-mediated dystrophin expression in a canine model of Duchenne 
      muscular dystrophy with a brief course of immunosuppression.
PG  - 1160-6
AB  - Adeno-associated virus-based vector (AAV)-mediated gene delivery has been 
      successful in some animal models of human disease such as the mdx mouse model of 
      human Duchenne muscular dystrophy (DMD). However, recent evidence of 
      immune-mediated loss of vector persistence in dogs and humans suggests that 
      immune modulation might be necessary to achieve successful long-term transgene 
      expression in these species. We have previously demonstrated that direct 
      intramuscular injection of AAV2 or AAV6 in wild-type random-bred dogs resulted in 
      a robust immune response to capsid or capsid-associated proteins. We now 
      demonstrate that a brief course of immunosuppression with a combination of 
      anti-thymocyte globulin (ATG), cyclosporine (CSP), and mycophenolate mofetil 
      (MMF) is sufficient to permit long-term and robust expression of a canine 
      micro-dystrophin (c-micro-dys) transgene in the skeletal muscle of a dog model 
      for DMD (canine X-linked muscular dystrophy, or cxmd dog) and that its expression 
      restored localization of components of the dystrophin-associated protein complex 
      at the muscle membrane. This protocol has potential applications to human 
      clinical trials to enhance AAV-mediated therapies.
FAU - Wang, Zejing
AU  - Wang Z
AD  - Program in Transplantation Biology, Division of Clinical Research, Fred 
      Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
FAU - Kuhr, Christian S
AU  - Kuhr CS
FAU - Allen, James M
AU  - Allen JM
FAU - Blankinship, Michael
AU  - Blankinship M
FAU - Gregorevic, Paul
AU  - Gregorevic P
FAU - Chamberlain, Jeffrey S
AU  - Chamberlain JS
FAU - Tapscott, Stephen J
AU  - Tapscott SJ
FAU - Storb, Rainer
AU  - Storb R
LA  - eng
GR  - CA15704/CA/NCI NIH HHS/United States
GR  - U54-HD47175/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070410
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (Dystrophin)
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
CIN - Mol Ther. 2007 Jun;15(6):1040-1. PMID: 17510638
MH  - Animals
MH  - Antilymphocyte Serum/pharmacology/therapeutic use
MH  - Cyclosporine/pharmacology/therapeutic use
MH  - Dependovirus/*genetics
MH  - Dogs
MH  - Drug Therapy, Combination
MH  - Dystrophin/*genetics/metabolism
MH  - Flow Cytometry
MH  - Gene Expression/drug effects
MH  - Genetic Therapy/methods
MH  - Genetic Vectors/genetics
MH  - Immunosuppression Therapy/*methods
MH  - Immunosuppressive Agents/pharmacology/therapeutic use
MH  - Muscle, Skeletal/drug effects/metabolism/pathology
MH  - Muscular Dystrophy, Animal/genetics/immunology/therapy
MH  - Muscular Dystrophy, Duchenne/genetics/immunology/*therapy
MH  - Mycophenolic Acid/analogs & derivatives/pharmacology/therapeutic use
EDAT- 2007/04/12 09:00
MHDA- 2007/09/26 09:00
CRDT- 2007/04/12 09:00
PHST- 2007/04/12 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2007/04/12 09:00 [entrez]
AID - S1525-0016(16)31675-6 [pii]
AID - 10.1038/sj.mt.6300161 [doi]
PST - ppublish
SO  - Mol Ther. 2007 Jun;15(6):1160-6. doi: 10.1038/sj.mt.6300161. Epub 2007 Apr 10.